Biomedical subjects

J S Skinner

Publications and source records attributed to J S Skinner.

At least 19 recordsLinked to original sources

PubMed2000

Linkage and association studies of the lipoprotein lipase gene with postheparin plasma lipase activities, body fat, and plasma lipid and lipoprotein concentrations: the HERITAGE Family Study.

Lipoprotein lipase (LPL) is responsible for the hydrolysis of triglyceride (TG)-rich lipoproteins. The aims of the present study were (1) to test for potential linkages (sib-pair method) between postheparin plasma lipase (lipoprotein and hepatic lipase) activities, body fatness, plasma lipid concentrations, and LPL polymorphisms (Ser447Ter and a tetranucleotide repeat) and microsatellite markers flanking the LPL locus (D8S261 and D8S258); and (2) to investigate associations between the LPL Ser447Ter (S447X) polymorphism and these phenotypes. Data on 190 parents and 312 adult offspring from 99 Caucasian families participating in the HERITAGE Family Study were available for this study. Data were adjusted for the effects of age within sex, and lipases, lipid variables, and abdominal visceral fat were further adjusted for fat mass. A suggestive linkage was observed only between the S447X polymorphism and very-low-density (VLDL)-apolipoprotein B (apo B) (332 sib-pairs, P = .013). The S447X polymorphism was not associated with body fat phenotypes or postheparin plasma LPL (PH-LPL) activity (men, P = .19; women, P = .47). In contrast, the X447 allele carriers had lower plasma TG (men and women, P = .01), VLDL-TG (men and women, P = .01), and VLDL-apo B (men and women, P = .009). The relationships between the X447 allele and plasma TG, VLDL-TG, and VLDL-apo B in both genders were observed in obese (body mass index [BMI] > or = 30 kg/m2) but not in normal-weight (BMI < 25 kg/m2) subjects. Thus, the S447X polymorphism of the LPL gene is not associated with body fatness and postheparin plasma lipase activities. However, the obese carriers of the X447 allele have plasma TG, VLDL-TG, and plasma cholesterol/high-density lipoprotein cholesterol (HDL-C) levels equivalent to those of normal-weight sedentary adults.

Adipose Tissue↗

PubMed2000

Blood lipid response to 20 weeks of supervised exercise in a large biracial population: the HERITAGE Family Study.

We studied the effects of 20 weeks of supervised cycle-ergometer exercise on plasma lipids in 675 healthy, sedentary, normolipidemic white and black men and women aged 17 to 65 years, participating in the HERITAGE Family Study. Fasting plasma lipids were assessed twice at baseline and 24 and 72 hours after the last exercise session and adjusted for plasma volume changes. No significant differences from the mean baseline levels were observed for total, low-density lipoprotein (LDL), and very-low-density lipoprotein (VLDL) cholesterol and apolipoprotein B (Apo B). A significant reduction (P < .01) from baseline levels in plasma total and VLDL triglycerides was observed only in the 24-hour posttraining specimens, reflecting a response to the last bout of exercise. High-density lipoprotein (HDL) cholesterol increased 3.6% for the combined group, primarily due to an increase in HDL2, with an associated increase in Apo A-1 (P < .001). No significant differences were noted in the HDL response by sex, race, or age. An inverse correlation (r = -.241) was observed between the increase in HDL cholesterol and change in body fat only in men, and the increase in HDL cholesterol was unrelated to the change in maximal oxygen uptake (VO2max).

Adolescent↗

PubMed2000

A genetic study of dehydroepiandrosterone sulfate measured before and after a 20-week endurance exercise training program: the HERITAGE Family Study.

Familial aggregation and possible major gene effects were evaluated for the baseline serum dehydroepiandrosterone sulfate (DHEAS) level and the change in DHEAS in response to a 20-week exercise training program in a sample of 481 individuals from 99 Caucasian families who were sedentary at baseline and who participated in the HERITAGE Family Study. Baseline DHEAS levels were not normally distributed, and were therefore logarithmically transformed and adjusted for the effects of age and sex prior to genetic analysis. The DHEAS response to training was computed as the simple difference, post-training minus baseline, and was adjusted for the baseline DHEAS level, age, and sex. Maximal (genetic and familial environmental) heritabilities (using a familial correlation model) reached 58% and 30% for the baseline and the response to training, respectively. Our estimate for the baseline is generally in agreement with previous reports, suggesting that the magnitude of the familial effect underlying this phenotype in these sedentary families is similar to that in the general population. However, segregation analysis showed no evidence for a multifactorial familial component in data for either the baseline or the response to training. Rather, a major additive gene controlling the baseline was found. For the response to training in the complete sample, transmission of the major effect from parents to offspring was ambiguous, but in a subset of 56 "responsive" families (with at least 1 family member whose response to training was greater than 1 standard deviation) this major effect was Mendelian in nature. The putative major genes accounted for 50% and 33% of the variance for the baseline and the response to training, respectively. The novel finding in this study is that the baseline DHEAS level and the change in DHEAS in response to training may be influenced by major gene effects.

Adult↗

PubMed2000

Familial aggregation of amount and distribution of subcutaneous fat and their responses to exercise training in the HERITAGE family study.

OBJECTIVE: Investigate the familial aggregation of amount and distribution of subcutaneous fat and their changes in response to endurance training. RESEARCH METHODS AND PROCEDURES: A total of 483 sedentary subjects from 99 nuclear families were recruited, trained for 20 weeks of exercising on cycle ergometers, and measured before and after training for the following indicators of subcutaneous fat and fat distribution: trunk fat (TRUNK = sum of abdominal, subscapular, suprailiac, and midaxillary skinfolds), extremity fat (EXTREM = sum of biceps, triceps, thigh, and calf skinfolds), subcutaneous fat (SF8 = sum of the eight skinfolds), the trunk to extremity skinfolds ratio adjusted for SF8 (TER) and waist girth adjusted for body mass index (WAIST). The familial aggregation of the age- and sex-adjusted baseline phenotypes and their responses to training (delta) after adjustment for the baseline values was investigated using a familial correlation model. RESULTS: Significant familial aggregation was observed for all the phenotypes measured at baseline and for deltaTRUNK and deltaWAIST. Transmissibility estimates reached about 30% to 35% for TRUNK, EXTREM, and SF8 and 50% for TER and WAIST. The transmissibilities of the response phenotypes were lower, ranging from 0% for deltaWAIST to 21% for deltaTRUNK and the pattern of familial correlations suggested a greater within- than between-generation resemblance in the response. DISCUSSION: This study suggests that the amount and distribution of subcutaneous fat strongly aggregates in families, whereas the response to exercise training is characterized by a moderate and more complex pattern of familial resemblance. We conclude that familial/genetic factors are more important in determining the amount and distribution of subcutaneous fat than their responses to exercise training.

Adipose Tissue↗

PubMed2000

Evidence of pleiotropic loci for fasting insulin, total fat mass, and abdominal visceral fat in a sedentary population: the HERITAGE family study.

OBJECTIVE: To examine whether there is a major gene effect on fasting insulin and pleiotropic loci for fasting insulin, total fat mass (FM), and abdominal visceral fat (AVF). RESEARCH METHODS AND PROCEDURES: A major gene hypothesis for fasting plasma insulin levels was assessed using segregation analyses of data on 495 members in 98 normolipidemic sedentary families of white descent who participated in the HERITAGE Family Study. RESULTS: Segregation analyses were performed on insulin adjusted for age, on insulin adjusted for age and FM, and on insulin adjusted for age and AVF. Before adjustment for AVF and FM, a major gene effect on fasting insulin levels was indicated. The putative locus accounted for 54% of the variance under a recessive inheritance pattern, affecting 11% of the sample (i.e., allele frequency = 0.33). However, after adjusting for the effects of AVF or FM, neither a major effect alone nor a multifactorial component alone could be rejected, and support for a major gene was equivocal, i.e., neither the hypothesis of Mendelian tau values or that of the equal tau(s) were rejected and the equal tau model fit the data better than the Mendelian tau model. This pattern (i.e., major gene evidence for insulin before but not after adjustment for AVF or FM) suggests that there is a putative locus with pleiotropic effects on both insulin and FM and another pleiotropic locus for both insulin and AVF. DISCUSSION: Although these data do not directly support an additional major gene for insulin independent of AVF and FM, such support cannot be ruled out because there is still a significant major effect on FM- or AVF-adjusted insulin (albeit the Mendelian nature of this effect is ambiguous).

Abdomen↗

PubMed2000

Adaptation to a standardized training program and changes in fitness in a large, heterogeneous population: the HERITAGE Family Study.

PURPOSE: This paper describes the variations in response to a standardized, computer-controlled training program. METHODS: Steady-state heart rate (HR) and oxygen intake (VO2) of 614 healthy, sedentary men and women aged 16-65 yr were measured during three cycle ergometer exercise tests. The HR associated with 55, 65, 70, and 75% of each subject's pretraining VO2max was used to prescribe exercise intensity. Subjects exercised three times a week, beginning at a HR associated with 55% VO2max for 30 min. Duration and intensity was gradually increased over 20 wk of training. The duration and HR of each training session were controlled by a computer. RESULTS: Using the linear relationship between HR, VO2 and power output (PO), PO were predicted for each of 60 training sessions at the respective programmed HR. The average ratio of the actual training HR to programmed HR was 0.99. It was hypothesized that participants whose actual training PO exceeded their predicted PO would improve VO2max more than those whose actual PO was less than their predicted PO. Using the ratio of actual/predicted PO determined after the training was over, participants were arbitrarily assigned to three groups: 128 participants had low (LO) ratios (0.65-0.84), 408 had average (AV) ratios (0.85-1.14), and 78 had high (HI) ratios (1.15-1.34). Secondary analysis showed that the training program significantly increased mean VO2max of all three groups. Those who had a smaller increase in training PO (LO) had significantly less increase in VO2max than those with larger increases in PO (HI). CONCLUSION: People who exercise at a HR associated with the same %VO2max can vary substantially in their training PO, in their rate of increase in PO over a 20-wk training program, and in improvement of their VO2max.

Adaptation, Physiological↗

PubMed2000

The Na(+)-K(+)-ATPase alpha2 gene and trainability of cardiorespiratory endurance: the HERITAGE family study.

The Na(+)-K(+)-ATPase plays an important role in the maintenance of electrolyte balance in the working muscle and thus may contribute to endurance performance. This study aimed to investigate the associations between genetic variants at the Na(+)-K(+)-ATPase alpha2 locus and the response (Delta) of maximal oxygen consumption (VO(2 max)) and maximal power output (W(max)) to 20 wk of endurance training in 472 sedentary Caucasian subjects from 99 families. VO(2 max) and W(max) were measured during two maximal cycle ergometer exercise tests before and again after the training program, and restriction fragment length polymorphisms at the Na(+)-K(+)-ATPase alpha2 (exons 1 and 21-22 with Bgl II) gene were typed. Sibling-pair linkage analysis revealed marginal evidence for linkage between the alpha2 haplotype and DeltaVO(2 max) (P = 0.054) and stronger linkages between the alpha2 exon 21-22 marker (P = 0.005) and alpha2 haplotype (P = 0.003) and DeltaW(max). In the whole cohort, DeltaVO(2 max) in the 3.3-kb homozygotes of the exon 1 marker (n = 5) was 41% lower than in the 8.0/3.3-kb heterozygotes (n = 87) and 48% lower than in the 8.0-kb homozygotes (n = 380; P = 0.018, adjusted for age, gender, baseline VO(2 max), and body weight). Among offspring, 10.5/10.5-kb homozygotes (n = 14) of the exon 21-22 marker showed a 571 +/- 56 (SE) ml O(2)/min increase in VO(2 max), whereas the increases in the 10.5/4.3-kb (n = 93) and 4.3/4.3-kb (n = 187) genotypes were 442 +/- 22 and 410 +/- 15 ml O(2)/min, respectively (P = 0.017). These data suggest that genetic variation at the Na(+)-K(+)-ATPase alpha2 locus influences the trainability of VO(2 max) in sedentary Caucasian subjects.

Adaptation, Physiological↗

PubMed2000

Genomic scan for maximal oxygen uptake and its response to training in the HERITAGE Family Study.

This study aimed to identify human genomic regions that are linked to maximal oxygen uptake (VO(2 max)) in sedentary individuals or to the responsiveness of VO(2 max) to a standardized endurance training program. The results of a genomic scan based on 289 polymorphic markers covering all 22 pairs of autosomes performed on the Caucasian families of the HERITAGE Family Study are presented. The mean spacing of the markers was 11 cM, and a total of 99 families and 415 pairs of siblings were available for the study. VO(2 max) in the sedentary state was adjusted for the effects of age, sex, body mass, fat mass, and fat-free mass, whereas the VO(2 max) response was adjusted for age and baseline level of the phenotype. Two analytic strategies were used: a single-point linkage procedure using all available pairs of siblings (SIBPAL) and a multipoint variance components approach using all the family data (SEGPATH). Results indicate that linkages at P values of 0.01 and better are observed with markers on 4q, 8q, 11p, and 14q for VO(2 max) before training and with markers on 1p, 2p, 4q, 6p, and 11p for the change in VO(2 max) in response to a 20-wk standardized endurance training program. These chromosomal regions harbor many genes that may qualify as candidate genes for these quantitative traits. They should be investigated in this and other cohorts.

Adolescent↗

PubMed2000

Angiotensin-converting enzyme ID polymorphism and fitness phenotype in the HERITAGE Family Study.

It has been suggested that genetic variation in the angiotensin-converting enzyme (ACE) gene is associated with physical performance. We studied the association between the ACE insertion (I)/deletion (D) polymorphism and several fitness phenotypes measured before and after 20 wk of a standardized endurance training program in sedentary Caucasian (n = 476) and black (n = 248) subjects. Phenotypes measured were oxygen uptake (VO(2)), work rate, heart rate, minute ventilation, tidal volume, and blood lactate levels during maximal and submaximal [50 W and at 60 and 80% of maximal VO(2) (VO(2 max))] exercise and stroke volume and cardiac output during submaximal exercise (50 W and at 60% VO(2 max)). The ACE ID polymorphism was typed with the three-primer PCR method. Out of 216 association tests performed on 54 phenotypes in 4 groups of participants, only 11 showed significant (P values from 0.042 to 0. 0001) associations with the ACE ID polymorphism. In contrast to previous claims, in Caucasian offspring, the DD homozygotes showed a 14-38% greater increase with training in VO(2 max), VO(2) at 80% of VO(2 max), and all work rate phenotypes and a 36% greater decrease in heart rate at 50 W than did the II homozygotes. No associations were evident in Caucasian parents or black parents or offspring. Thus these data do not support the hypothesis that the ACE ID polymorphism plays a major role in cardiorespiratory endurance.

Adult↗

PubMed2000

Segregation analysis of apolipoproteins A-1 and B-100 measured before and after an exercise training program: the HERITAGE Family Study.

Complex segregation analyses of apolipoproteins (apo) A-1 and B-100 were performed in a sample of 520 individuals from 99 white families who participated in the HERITAGE Family Study. In these sedentary families, plasma apo A-1 and B-100 concentrations were measured before and after a 20-week endurance exercise training program. Baseline apo A-1 and B-100 were adjusted for the effects of age (age-adjusted baseline apo A-1 and B-100) and for the effects of age and BMI (age-BMI-adjusted baseline apo A-1 and B-100). The change in response to training was computed as a simple Delta (posttraining minus baseline) and was adjusted for age and the baseline (age-baseline-adjusted apo A-1 and B-100 responses to training). In the present study, a major gene could not be inferred for baseline apo A-1. Rather, we found a major effect along with a multifactorial effect accounting for 8% to 9% and 51% to 56% of the variance, respectively. In addition, no clear evidence supported a major-gene effect for its response to training, whereas the transmission of a major effect from parents to offspring was ambiguous, ie, genetic in nature or familial environmental in origin. The major effect accounted for 15% of the variance, with an additional 21% and 58% of the variance being accounted for by a multifactorial effect in parents and offspring, respectively. It is interesting to have obtained evidence of a putative recessive major locus for baseline apo B-100, which accounted for 50% to 56% of the variance, with an additional 25% to 29% of the variance due to a multifactorial effect. In contrast, no major effect for its response to training was identified, although a multifactorial effect was found that accounted for 27% of the variance. The novel findings arising from the present study are summarized as follows. Baseline apo A-1 and its response to training were influenced by a major effect and a multifactorial effect. Baseline apo B-100 was influenced by a putative major recessive gene with a multifactorial component, but its response to training was influenced solely by a multifactorial component in these sedentary families.

Adolescent↗

PubMed2000

Associations between the leptin receptor gene and adiposity in middle-aged Caucasian males from the HERITAGE family study.

Linkage and association studies between three exonic polymorphisms in the leptin receptor gene and body composition variables in the HERITAGE Family Study were undertaken. Polymorphisms K109R, Q223R, and K656N have been analyzed with body mass index (BMI), sum of height skinfolds (SF8), fat mass (FM), percent body fat (%FAT), fat free mass, and plasma leptin level. Single-point linkage analysis and covariance analysis across genotypes were performed, by race, on phenotypes adjusted for age and sex. Blacks (88 parents; 231 adult offspring) from 115 nuclear families (72-119 sibpairs) and Caucasians (192 parents; 330 adult offspring) from 99 nuclear families (319-364 sibpairs) were used for these analyses. In Caucasians, BMI and FM showed suggestive linkages with K109R (P = 0.02 and P = 0.05, respectively) and associations with Q223R (P = 0.005 and P = 0.03, respectively). In blacks, no statistically significant linkage or association was observed. In Caucasians, associations with Q223R were observed in parents, but not in offspring, for BMI, FM, and %FAT (0.04< or =P< or =0.0001). Males, not females, showed differences across genotypes for the same phenotypes plus SF8 and leptin (0.03< or = P< or =0.0002). Carriers of the R223 allele showed higher values than noncarriers for BMI (+4 U, P = 0.0001), SF8 (+30 mm, P = 0.01), FM (+7 kg, P = 0.0004), %FAT (+5%, P = 0.0002), and leptin (+4 ng/mL, P = 0.0006). These results indicate a significant effect of leptin receptor on adiposity in middle-aged Caucasian males.

Adipose Tissue↗

PubMed2000

Contribution of body fatness and adipose tissue distribution to the age variation in plasma steroid hormone concentrations in men: the HERITAGE Family Study.

Obesity has been associated with alterations in plasma steroid hormone concentrations in men. Older men present an altered steroid hormone profile compared to younger individuals, and an increase in body fatness and changes in adipose tissue (AT) distribution are noted with advancing age. Thus, there is a need to examine the relative importance of increased body fatness and changes in AT distribution with advancing age to plasma steroid hormone and sex hormone-binding globulin levels in men. We, therefore, investigated the relationships among age, body fatness, AT distribution, and the plasma steroid hormone profile in a group of 217 Caucasian men (mean age +/- SD, 36.2 +/- 14.9 yr) who covered a wide age range (17-64 yr). Compared to young adult men, older men were characterized by increased adiposity (P < 0.0001) expressed either as body mass index or total body fat mass assessed by underwater weighing. Differences in AT distribution were also noted with a preferential accumulation of abdominal fat as indicated by a larger waist girth (P < 0.0001) and higher visceral AT accumulation (P < 0.0001), measured by computed tomography, in older subjects. Age was associated with decreases (P < 0.0001) in C19 adrenal steroid levels, namely reduced dehydroepiandrosterone (DHEA), DHEA fatty acid ester, DHEA sulfate, as well as androstenedione levels. Androgens, i.e. dihydrotestosterone and testosterone, were also affected by age, with lower levels of both steroids being found in older individuals (P < 0.0005). When statistical adjustment for body fatness and AT distribution was performed, differences in C19 adrenal steroids between the age groups remained significant, whereas differences in androgens and sex hormone-binding globulin concentrations were no longer significant. The present study suggests that age-related differences in plasma steroid hormone levels, especially androgens, are partly mediated by concomitant variation in adiposity in men.

Adipose Tissue↗

PubMed2000

Associations among hospital capacity, utilization, and mortality of US Medicare beneficiaries, controlling for sociodemographic factors.

OBJECTIVE: To explore whether geographic variations in Medicare hospital utilization rates are due to differences in local hospital capacity, after controlling for socioeconomic status and disease burden, and to determine whether greater hospital capacity is associated with lower Medicare mortality rates. DATA SOURCES/STUDY SETTING: The study population: a 20 percent sample of 1989 Medicare enrollees. Measures of resources were based on a national small area analysis of 313 Hospital Referral Regions (HRR). Demographic and socioeconomic data were obtained from the 1990 U.S. Census. Measures of local disease burden were developed using Medicare claims files. STUDY DESIGN: The study was a cross-sectional analysis of the relationship between per capita measures of hospital resources in each region and hospital utilization and mortality rates among Medicare enrollees. Regression techniques were used to control for differences in sociodemographic characteristics and disease burden across areas. DATA COLLECTION/EXTRACTION METHODS: Data on the study population were obtained from Medicare enrollment (Denominator File) and hospital claims files (MedPAR) and U.S. Census files. PRINCIPAL FINDINGS: The per capita supply of hospital beds varied by more than twofold across U.S. regions. Residents of areas with more beds were up to 30 percent more likely to be hospitalized, controlling for ecologic measures of socioeconomic characteristics and disease burden. A greater proportion of the population was hospitalized at least once during the year in areas with more beds; death was also more likely to take place in an inpatient setting. All effects were consistent across racial and income groups. Residence in areas with greater levels of hospital resources was not associated with a decreased risk of death. CONCLUSIONS: Residence in areas of greater hospital capacity is associated with substantially increased use of the hospital, even after controlling for socioeconomic characteristics and illness burden. This increased use provides no detectable mortality benefit.

Aged↗

PubMed1999

The association between for-profit hospital ownership and increased Medicare spending.

BACKGROUND AND METHODS: The rate of conversion to for-profit ownership of hospitals has recently increased in the United States, with uncertain implications for health care costs. We compared total per capita Medicare spending in areas served by for-profit and not-for-profit hospitals. We used American Hospital Association data to categorize U.S. hospital service areas as for-profit (meaning that all beds in the area were in for-profit hospitals), not-for-profit (all beds were in not-for-profit hospitals), or mixed in 1989, 1992, and 1995. We then used data from the Continuous Medicare History Sample to calculate the 1989, 1992, and 1995 spending rates in each area, adjusting for other characteristics known to influence spending: age, sex, race, region of the United States, percentage of population living in urban areas, Medicare mortality rate, number of hospitals, number of physicians per capita, percentage of beds in hospitals affiliated with medical schools, percentage of beds in hospitals belonging to hospital chains, and percentage of Medicare beneficiaries enrolled in health maintenance organizations. RESULTS: Adjusted total per capita Medicare spending in the 208 areas where all hospitals remained under for-profit ownership during the study years was greater than in the 2860 areas where all hospitals remained under not-for-profit ownership ($4,006 vs. $3,554 in 1989, $4,243 vs. $3,841 in 1992, and $5,172 vs. $4,440 in 1995; P<0.001 for each comparison). Mixed areas had intermediate spending rates. Spending in for-profit areas was greater than in not-for-profit areas in each category of service examined: hospital services, physicians' services, home health care, and services at other facilities. The greatest increases in per capita spending between 1989 and 1995 were for hospital services (a mean increase of $395 in for-profit areas and $283 in not-for-profit areas, P=0.03 for the comparison between for-profit and not-for-profit areas) and home health care (an increase of $457 in for-profit areas and $324 in not-for-profit areas, P<0.001). Between 1989 and 1995, spending in the 33 areas where all hospitals converted from not-for-profit to for-profit ownership grew more rapidly than in the 2860 areas where all hospitals remained under not-for-profit ownership ($1,295 vs. $866, P=0.03). CONCLUSIONS: Both the rates of per capita Medicare spending and the increases in spending rates were greater in areas served by for-profit hospitals than in areas served by not-for-profit hospitals.

Health Expenditures↗

PubMed1999

Body fat, resting and exercise blood pressure and the angiotensinogen M235T polymorphism: the heritage family study.

OBJECTIVE: The association of resting and exercise blood pressure (BP) and fat mass with the angiotensinogen (AGT) M235T polymorphism was investigated in 522 sedentary Caucasian subjects from 99 families. RESEARCH METHODS AND PROCEDURES: Resting BP was measured on two separate days, three times each day, and the mean of six valid measurements was used. Exercise BP was measured during a cycle ergometer test at a constant power output (50 W). Body composition was derived from under-water weighing and the AGT M235T polymorphism was typed with a polymerase chain reaction-based method. RESULTS: Neither resting nor exercise BP was associated with the AGT genotypes. In mothers, the homozygotes for the T allele showed 8.8 kg and 7.1 kg greater (p=0.017) age-adjusted body fat mass (FM) than the MM homozygotes and heterozygotes, respectively. Sixty-nine percent of all TT homozygotes were found in the highest FM tertile, whereas only 16% of the MM homozygotes fell in the same tertile (p = 0.008). Moreover, a significant interaction was seen between FM and T-allele carrier status in women with regard to resting diastolic BP (p = 0.002). Among women with a FM> or =24 kg, carriers of the T allele showed a 6.3 mmHg higher diastolic blood pressure (DBP) than non-carriers whereas no difference was found in women with a FM less than 24 kg. A similar trend toward an interaction term was evident with resting systolic blood pressure (p = 0.011) and exercise DBP (p = 0.012). Body fat was not associated with the AGT polymorphism in fathers or in offspring. DISCUSSION: These data suggest that the AGT M235T polymorphism is associated with body fatness in women, and that the relationship between DBP and AGT M235T polymorphism is dependent on FM in middle-aged sedentary normotensive women.

Adipose Tissue↗

PubMed1999

Plasma post-heparin lipase activities in the HERITAGE Family Study: the reproducibility, gender differences, and associations with lipoprotein levels. HEalth, RIsk factors, exercise Training and GEnetics.

OBJECTIVES: Examine the reproducibility of plasma lipid and lipoprotein measurements in the HERITAGE Family Study. DESIGN AND METHODS: In a sample of 379 subjects (191 men and 188 women), reproducibility was determined for lipids, lipoproteins (done on two occasions) and post-heparin lipase assays using an Intracenter Quality Control study by generating split samples from an additional 60 subjects (35 men and 25 women), which were assayed in a blind fashion by the lipid core laboratory. Reproducibility was estimated using intraclass correlation coefficients (ICC) for the selected variables. Analytical error (ANER) and coefficient of variation (CV) were also calculated. Day-to-day variation for 10 variables including plasma cholesterol and triglycerides (TG), HDL-cholesterol and its subfractions HDL2-cholesterol and HDL3-cholesterol, LDL-cholesterol and VLDL-cholesterol, as well as apoprotein (apo) A-I, apo B, and LDL-apo B were assessed. RESULTS: In the HERITAGE study, all lipid and lipoprotein variables had ICC above 0.79. Plasma VLDL-cholesterol (31 %) and TG (23%) levels, which are well known to be highly variable from one day to another, had CVs greater than 20%. Other variables had CVs lower than 10% except for HDL2-cholesterol which reached 16%. In the intracenter reliability sub-study, the measurement errors were found to be low except for HDL2-cholesterol. For the lipases, the reproducibility of repeated samples was very high, with ICC over 0.95. The within-assay CV corresponded to 2.1 and 5.3% for hepatic lipase (HL) and lipoprotein lipase (LPL), respectively, whereas the between-assay CV reached 8-12% for HL and about 15% for LPL. Due to the complexity of these two assays, the results are considered to be quite satisfactory. CONCLUSIONS: The reproducibility of plasma lipid and lipoprotein measurements, as well as of post-heparin lipase activities, is good in the multicenter HERITAGE Family Study. In addition, the well-documented gender difference in the plasma lipoprotein profile was confirmed in the present study, women having lower fasting triglyceride and LDL-cholesterol levels than men as well as reduced cholesterol/HDL-cholesterol and increased HDL2-cholesterol/ HDL3-cholesterol ratios compared to men. Results of the present study support the notion that the higher LPL and low HL activities found in women compared to men are important factors contributing to explain gender difference in the lipoprotein profile. However, additional factors not examined in the present study are involved beyond the contribution of post-heparin lipase to the sex dimorphism in plasma lipoprotein levels.

Female↗

PubMed1999

Evidence of a major locus for lipoprotein lipase (LPL) activity in addition to a pleiotropic locus for both LPL and fasting insulin: results from the HERITAGE Family Study.

A major gene hypothesis for heparin releasable plasma lipoprotein lipase (PH-LPL) activity was assessed using segregation analyses of data on 495 members in 98 normolipidemic sedentary families of Caucasian descent who participated in the HERITAGE Family Study. Segregation analyses were performed on PH-LPL adjusted for age, and on PH-LPL activity adjusted for age and fasting insulin. Prior to adjustment for insulin, neither a major gene effect nor a multifactorial component could be rejected, and support for a major gene was equivocal i.e. neither the Mendelian transmission nor the no transmission (equal tau s) models were rejected. However, after adjusting for the effects of insulin, a major gene effect on PH-LPL activity was unambiguous. The putative locus accounted for 60% of the total phenotypic variance, and the homozygous recessive form affected 10% (q2) of the sample (i.e. gene frequency (q) = 0.31), and led to a low PH-LPL value. The lack of a significant multifactorial effect suggested that the familial etiology of PH-LPL activity adjusted for insulin was likely to be primarily a function of the major locus. In conclusion, the present study is the first to report segregation analyses on PH-LPL activity prior to and after adjusting for insulin, and suggests that there is an indication of a pleiotropic genetic effect on PH-LPL activity and insulin, in addition to a major gene effect on PH-LPL activity alone.

Adolescent↗

PubMed1999

Total body fat and abdominal visceral fat response to exercise training in the HERITAGE Family Study: evidence for major locus but no multifactorial effects.

The familial etiology of the response in total fat mass (FM) and abdominal visceral fat (AVF) to 20 weeks of exercise training was investigated in families participating in the HERITAGE Family Study. AVF (measured by computed tomographic scanning) and FM (measured by underwater weighing techniques) were assessed at baseline (in a sedentary state) and after 20 weeks of exercise training. The response AVF (AVFdelta) and response FM (FMdelta) were computed as the simple delta values (posttraining - baseline) and adjusted for the effects of sex, generation, and a polynomial in age using multiple regression analysis. To index the AVF response independently of the response in FM and the initial level of visceral fat, the AVFdelta was also adjusted for age and baseline AVF (AVFB) and FMdelta. Familial correlation analysis was used to investigate the multifactorial familial effects (polygenic and/or familial environmental), and segregation analysis was used to search for major gene effects. For the age-adjusted AVFdelta, a putative recessive locus accounting for 18% of the variance (q2 = 1%) was detected. Adjusting AVFdelta for AVFB and FMdelta slightly increased the percentage of variance accounted for (to 26%, q2 = 3%) but did not radically alter the pattern of the parameter estimates. For FMdelta, a putative dominant locus accounting for 31% of the variance (q2 = 49%) was noted. In conclusion, the results were consistent across methods in suggesting that there is little evidence of a multifactorial heritability for either AVFdelta or FMdelta. Rather, the familial etiology of the response to exercise training appears to be primarily due to putative major genes (a recessive locus for AVFdelta and a dominant locus for FMdelta). In addition, a pleiotropic/oligogenic system underlying these variables was inferred. That is, the putative loci for FMdelta and/or AVFB also may impact the AVFdelta, with an additional independent major locus effect on AVFdelta after the former influences have been removed.

Abdomen↗