Biomedical subjects

D C Rao

Publications and source records attributed to D C Rao.

At least 163 records · Page 9Linked to original sources

PubMed2001

Age, body mass index, race and other determinants of steroid hormone variability: the HERITAGE Family Study.

OBJECTIVE AND METHODS: To investigate from the HERITAGE Family Study database, 13 steroid hormones (androstane-3alpha, 17beta-diol glucuronide, androsterone glucuronide, cortisol, dehydroepiandrosterone (DHEA), DHEA ester (DHEAE), DHEA sulfate (DHEAS), dihydrotestosterone (DHT), estradiol, 17-hydroxyprogesterone, progesterone, pregnenolone ester, sex hormone binding globulin (SHBG) and testosterone in each sex for their relationships with age, body mass index (BMI), race and key lifestyle variables. Sample sizes varied from 676 to 750 per hormone. Incremental regression methods were used to examine the contributions of the variables to steroid hormone variability. RESULTS: Age was a major predictor for most steroid hormones. The greatest contribution of age was a negative relationship with DHEAS (R(2)=0.39). BMI was also associated with the variability of several steroid hormones, being the most important predictor of SHBG (R(2)=0.20) and of testosterone (R(2)=0.12) concentrations. When age and BMI were included, race still contributed significantly to the variations in cortisol (R(2)=0.02 for men and 0.04 for women), DHT (R(2)=0.02 for men and 0.03 for women), and progesterone (R(2)=0.03 for women). Nevertheless, race appeared to be less important than age and BMI. In addition, lifestyle indicators (food and nutrient intakes, smoking and physical activity) influenced steroid hormone variability. Their contributions, however, were minor in most cases once age, BMI and race had been taken into account. CONCLUSIONS: We conclude that age was the most important factor, followed by BMI, race and lifestyle factors in explaining steroid hormone variability.

Adolescent↗

PubMed2001

Familial resemblance for free androgens and androgen glucuronides in sedentary black and white individuals: the HERITAGE Family Study. Health, Risk Factors, Exercise Training and Genetics.

Familial correlation analyses were used to evaluate the familial aggregation of plasma androgens and androgen glucuronides (testosterone (TESTO), dihydrotestosterone (DHT), androstane-3 alpha,17 beta-diol glucuronide (3 alpha-DIOL-G), and androsterone glucuronide (ADT-G)) in 505 members of 99 white families and 296 members of 111 black families participating in the Health, Risk Factors, Exercise Training and Genetics (HERITAGE) Family Study. Each of these four measures was determined by RIA after separation of conjugated and unconjugated steroid using C18 column chromatography. All participants were sedentary prior to being including in this study. Significant spouse correlations, as well as parent-offspring and sibling correlations, were found for TESTO, DHT, 3 alpha-DIOL-G, and ADT-G in the white sample, suggesting that common familial environments and genes contribute to the familial resemblance. In the black sample, significant sibling and parent-offspring correlations were found for all four phenotypes, while the spouse correlation was marginally significant for 3 alpha-DIOL-G and not significant for TESTO, DHT, and ADT-G. The non-significance of spouse correlations in the black individuals may be due to the small number of spouse pairs. The maximal heritability estimates of TESTO, DHT, 3 alpha-DIOL-G, and ADT-G were 69%, 87%, 74%, and 56% for white individuals and 70%, 73%, 62%, and 48% for black individuals respectively. Sex differences in heritability estimates were found in the white individuals, but they were less dramatic in the black individuals. In conclusion, plasma levels of androgens and androgen glucuronides are highly heritable in both white individuals and black individuals. There are notable sex differences in the white individuals.

Adolescent↗

PubMed2001

A genome-wide scan for abdominal fat assessed by computed tomography in the Québec Family Study.

To identify chromosomal regions harboring genes influencing the propensity to store fat in the abdominal area, a genome-wide scan for abdominal fat was performed in the Quebec Family Study. Cross-sectional areas of the amount of abdominal total fat (ATF) and abdominal visceral fat (AVF) were assessed from a computed tomography scan taken at L4-L5 in 521 adult subjects. Abdominal subcutaneous fat (ASF) was obtained by computing the difference between ATF and AVF. The abdominal fat phenotypes were adjusted for age and sex effects as well as for total amount of body fat (kilogram of fat mass) measured by underwater weighing, and the adjusted phenotypes were used in linkage analyses. A total of 293 microsatellite markers spanning the 22 autosomal chromosomes were typed. The average intermarker distance was 11.9 cM. A maximum of 271 sib-pairs were available for single-point (SIBPAL) and 156 families for multipoint variance components (SEGPATH) linkage analyses. The strongest evidence of linkage was found on chromosome 12q24.3 between marker D12S2078 and ASF (logarithm of odds [LOD] = 2.88). Another marker (D12S1045) located within 2 cM of D12S2078 also provided evidence of sib-pair linkage with ASF (P = 0.019), ATF (P = 0.015), and AVF (P = 0.0007). Other regions with highly suggestive evidence (P < 0.0023 or LOD > or =1.75) of multipoint linkage and evidence (P < 0.05) of single-point linkage, all for ASF, included chromosomes 1p11.2, 4q32.1, 9q22.1, 12q22-q23, and 17q21.1. Three of these loci (1p11.2, 9q22.1, and 17q21.1) are close to genes involved in the regulation of sex steroid levels, whereas two others (4q32.1 and 17q21.1) are in the proximity of genes involved in the regulation of food intake. This first genome-wide scan for abdominal fat assessed by computed tomography indicates that there may be several loci determining the propensity to store fat in the abdominal depot and that some of these loci may influence the development of diabetes in obese subjects.

Adipose Tissue↗

PubMed2001

Decreased fasting and oral glucose stimulated C-peptide in nondiabetic subjects with sequence variants in the sulfonylurea receptor 1 gene.

The high-affinity sulfonylurea receptor 1 (SUR1) plays an important role in regulating insulin secretion. In the Québec Family Study, we genotyped 731 individuals (685 nondiabetic [ND] subjects) for the SUR1 gene IVS15-3c-->t and exon 18 Thr759(ACC-->ACT) polymorphisms using polymerase chain reaction-restriction fragment-length polymorphism analysis. Phenotypes measured were fasting plasma glucose (GLU), fasting plasma insulin (INS), and fasting C-peptide (CPEP), as well as oral glucose tolerance test (OGTT) responses; they were adjusted for age, sex, waist circumference, and the sum of six skinfold thicknesses. In ND subjects, exon 18 Thr759(ACC-->ACT) T allele carriers (T+) had lower CPEP (P = 0.022, -12.8%) and acute C-peptide responses (area above basal in first 30 min [CP30]) (P = 0.051, -12.4%) than noncarriers (T-). Also, in those with the cT/tC haplotype (from both IVS15-3c-->t and exon 18 Thr759[ACC-->ACT] polymorphisms), CPEP (P = 0.005, -21.2%), CP30 (P = 0.034, -19.2%), and total C-peptide responses (P = 0.016, -20.2%) were lower than that in cT- subjects. In overweight individuals (BMI >25 kg/m2), differences between carriers and noncarriers of the T or cT alleles were greater for GLU (P = 0.023-0.034), CPEP (P = 0.021-0.015), acute OGTT insulin response (P = 0.014-0.019), and CP30 (P = 0.034-0.019). These results suggest that the T and cT allele variants are associated with lower insulin secretion parameters, particularly in female and overweight subjects, adding evidence to the role of SUR1 sequence variants in decreased insulin secretion.

ATP-Binding Cassette Transporters↗

PubMed2001

Familial aggregation of seven-year changes in blood pressure in Canada.

OBJECTIVE: To determine the familial resemblance for baseline and seven-year changes in blood pressure in the Canadian population. METHODS: The study participants were 857 people from 348 families in the 1988 Campbell's Survey, which was a seven-year follow-up of the Canada Fitness Survey. Systolic and diastolic blood pressures were measured at baseline and at follow-up, and were adjusted for age and body mass index by using regression analysis. Familial correlation models were fit to the data by using path analysis, and maximal heritabilities were calculated from the most parsimonious models. RESULTS: There was significant familial resemblance for baseline blood pressure and changes in blood pressure. In general, all classes of familial correlations (spousal, parent-offspring and sibling) were significant and were of comparable magnitude. The maximal heritabilities, which are influenced to an unknown degree by genes and shared environmental factors, were 50% and 70% for diastolic and systolic blood pressures, respectively, and 66% and 41% for seven-year changes in diastolic and systolic blood pressures, respectively. CONCLUSIONS: There is significant familial aggregation for blood pressure and for natural changes in blood pressure in the Canadian population. Genes may be important in explaining the familial resemblance for blood pressure; however, the presence of significant spousal correlations suggests that shared lifestyle and family environments are also important factors in the familial aggregation.

Adolescent↗

PubMed2000

Genome-wide linkage analysis of systolic and diastolic blood pressure: the Québec Family Study.

BACKGROUND: Blood pressure (BP), an important risk factor for coronary heart disease, is a complex trait with multiple genetic etiologies. While some loci affecting BP variation are known (eg, angiotensinogen), there are likely to be novel signals that can be detected with a genome scan approach. METHODS AND RESULTS: A genome-wide scan was performed in 125 random and 81 obese families participating in the Québec Family Study. A multipoint variance-components linkage analysis of 420 markers (353 microsatellites and 67 restriction fragment length polymorphisms) revealed several signals (P:<0.0023) for systolic BP on 1p (D1S551, ATP1A1), 2p (D2S1790, D2S2972), 5p (D5S1986), 7q (D7S530), 8q (CRH), and 19p (D19S247). Suggestive evidence (0.0023<P:<0.01) was found on 3q, 10p, 12p, 14q, and 22q. The results were encouraging for HSD3B1 (P:<0.03), AGT (P:<0.03), ACE (P:<0.02), and adipsin (P:<0.005) but null with regard to other candidates (eg, renin, and glucocorticoid and adrenergic receptors). CONCLUSIONS: Multiple linkage regions support the notion that risk for hypertension is due to multiple (ie, oligogenic) susceptibility loci. Comparisons across the complete, random, and obese samples suggest that some regions are specific to BP and others may involve obesity (eg, pleiotropy, epistasis, or gene-environment interaction). Some of these areas harbor known candidates. Others involve novel regions, some of which replicate previous reports and provide a focus for future studies to identify novel genes that influence interindividual variation in BP.

Age Distribution↗

PubMed2000

Segregation analysis of serum uric acid in the NHLBI Family Heart Study.

Segregation analysis was performed on the serum uric acid measurements from 523 randomly ascertained Caucasian families from the NHLBI Family Heart Study. Gender-specific standardized residuals were used as the phenotypic variable in both familial correlation and segregation analysis. Uric acid residuals were adjusted for age, age2, age3, body mass index (kg/m2), creatinine level, aspirin use (yes/no), total drinks (per week), HOMA insulin resistance index [(glucose * insulin)/22.5], diuretic use (yes/no), and triglyceride level. Sibling correlations (r=0.193) and parent-offspring correlations (r=0.217) were significantly different from zero, but these two familial correlations were not significantly different from one another. After adjustment for covariates, the heritability estimate for serum uric acid was 0.399. Segregation analysis rejected the "no major gene" model but was unable to discriminate between an "environmental" and a "Mendelian major gene" model. These results support the hypothesis that uric acid is a multifactorial trait possibly influenced by more than one major gene, modifying genes, and environmental factors.

Arteriosclerosis↗

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

Genome-wide search for genes related to the fat-free body mass in the Québec family study.

Fat-free mass (FFM) consists mostly of skeletal muscle and bone tissues, and identification of the genes and molecular mechanisms involved in the control of FFM would have implications for the understanding of sarcopenia and potentially osteoporesis associated with aging, as well as the response to starvation, refeeding, anorexia, and any other conditions in which lean body mass is important. A genome-wide search for genes related to body leanness has been completed in the Quebec Family Study (QFS). Microsatellite markers (N = 292) from the 22 autosomal chromosomes were typed. The mean spacing of the markers was 11.9 centimorgans (cM) (range, <0.1 to 41). FFM was calculated from percent body fat, derived from underwater weighing, and body weight and was adjusted by regression for age and sex effects before analysis. A maximum of 336 sib pairs or 609 pairs of extended relatives were analyzed using single-point Haseman-Elston regression (SIBPAL and RELPAL) and multipoint variance component (SEGPATH) linkage analyses. Significant linkages were observed on chromosomes 15q25-q26 for a CA repeat within the insulin-like growth factor 1 receptor (IGF1R) gene (Lod score = 3.56) and at 18q12 with D18S877 (Lod score = 3.53) and D18S535 (Lod score = 3.58), 2 markers located 10 cM apart. A moderately significant linkage was also observed on chromosome 7p15.3 with the marker D7S1808 (Lod score = 2.72). The most obvious candidate genes within the regions identified by these linkages include the IGF1R on 15q and neuropeptide Y (NPY) and growth hormone-releasing hormone (GHRH) receptor on 7p. On 18q, the melanocortin receptor 4 (MC4R) is not likely the candidate gene for the observed linkage. This study represents the first genome-wide search for genes that may be involved in the regulation of the lean component of body mass in humans.

Adult↗

PubMed2000

Complex segregation analysis of blood pressure and heart rate measured before and after a 20-week endurance exercise training program: the HERITAGE Family Study.

Complex segregation analysis of baseline resting blood pressure (BP) and heart rate (HR) and their responses to training (post-training minus baseline) were performed in a sample of 482 individuals from 99 white families who participated in the HERITAGE Family Study. Resting BP and HR were measured at baseline and after a 20-week training program. Baseline resting BP and HR were age-adjusted and age-BMI-adjusted, and the responses to training were age-adjusted and age-baseline-adjusted, within four gender-by-generation groups. This study also analyzed the responses to training in two subsets of families: (1) the so-called "high" subsample, 45 families (216 individuals) with at least one member whose baseline resting BP is in the high end of the normal BP range (the upper 95th percentile: systolic BP [SBP] > or = 135 or diastolic BP [DBP] > or = 80 mm Hg); and (2) the so-called "nonhigh" subsample, the 54 remaining families (266 individuals). Baseline resting SBP was influenced by a multifactorial component (23%), which was independent of body mass index (BMI). Baseline resting DBP was influenced by a putative recessive locus, which accounted for 31% of the variance. In addition to the major gene effect, which may impact BMI as well, baseline resting DBP was also influenced by a multifactorial component (29%). Baseline resting HR was influenced by a putative dominant locus independent of BMI, which accounted for 31% of the variance. For the responses to training, no familiality was found in the whole sample or in the nonhigh subsample. However, in the high subsample, resting SBP response to training was influenced by a putative recessive locus, which accounted for 44% of the variance. No familiality was found for resting DBP response to training. Resting HR response to training was influenced by a major effect (accounting for 35% of the variance), with an ambiguous transmission from parents to offspring.

Adolescent↗

PubMed2000

Reproducibility of resting blood pressure and heart rate measurements. The HERITAGE Family Study.

PURPOSE: This study determined the reproducibility of resting systolic and diastolic blood pressure, mean arterial pressure, and heart rate (the average of three measures/day). METHODS: The data were obtained on two separate days prior to an exercise training intervention in a sample of 822 subjects participating in the HERITAGE Family Study. The same protocol was conducted across three days in an intracenter quality control substudy, which included an additional 60 subjects. RESULTS: Reproducibility estimates included technical error, coefficient of variation within subjects, and intraclass correlation with results expressed by sex, race, age, cuff size, BMI, and %fat. Since the data were collected across four Clinical Centers, the reproducibility estimates were also computed separately for each Center. The systolic, diastolic, and mean arterial blood pressures were highly reproducible with technical errors less than 5.1 mmHg, coefficients of variation of less than 7. 0% and intraclass correlations > 0.75. The heart rates were slightly less reproducible. These results were fairly consistent across subject populations and across all four Clinical Centers. CONCLUSION: It is concluded that within subject day-to-day variations are small compared to between subject variance for resting systolic, diastolic, and mean arterial blood pressure and heart rate at each of the Clinical Centers for all of the HERITAGE Family Study data. This makes it appropriate to pool the data and analyze it for changes subsequent to endurance exercise training and to determine the possible genetic basis for these changes.

Adolescent↗

PubMed2000

NHLBI family blood pressure program: methodology and recruitment in the HyperGEN network. Hypertension genetic epidemiology network.

PURPOSE: Hypertension is a common precursor of serious disorders including stroke, myocardial infarction, congestive heart failure, and renal failure in whites and to a greater extent in African Americans. Large genetic-epidemiological studies of hypertension are needed to gain information that will improve future methods for diagnosis, treatment, and prevention of hypertension, a major contributor to cardiovascular morbidity and mortality. METHODS: We report successful implementation of a new structure of research collaboration involving four NHLBI "Networks," coordinated under the Family Blood Pressure Program. The Hypertension Genetic Epidemiology Network (HyperGEN) involves scientists from six universities and the NHLBI who seek to identify and characterize genes promoting hypertension. Blood samples and clinical data were projected to be collected from a sample of 2244 hypertensive siblings diagnosed before age 60 from 960 sibships (half African-American) with two or more affected persons. Nonparametric sibship linkage analysis of over one million genotype determinations (20 candidate loci and 387 anonymous marker loci) was projected to have sufficient power for detecting genetic loci promoting hypertension. For loci showing evidence for linkage in this study and for loci reported linked or associated with hypertension by other groups, genotypes are compared in hypertensive cases versus population-based controls to identify or confirm genetic variants associated with hypertension. For some of these genetic variants associated with hypertension, detailed physiological and biochemical characterization of untreated adult offspring carriers versus non-carriers may help elucidate the pathophysiological mechanisms that promote hypertension. RESULTS: The projected sample size of 2244 hypertensive participants was surpassed, as 2407 hypertensive individuals (1262 African-Americans and 1145 whites) from 917 sibships were examined. Detailed consent forms were designed to offer participants several options for DNA testing; 94% of participants gave permission for DNA testing now or in the future for any confidential medical research, with only 6% requesting restrictions for tests performed on their DNA. Since this is a family study, participants also are asked to list all first degree relatives (along with names, addresses, and phone numbers) and to indicate for each relative whether they were willing to allow study staff to make a contact. Seventy percent gave permission to contact some relatives; about 30% gave permission to contact all first degree relatives; and less than 1% asked that no relatives be contacted. Successes after the first four years of this study include: 1) productive collaboration of eight centers from six different locations; 2) early achievement of recruitment goals for study participants including African-Americans; 3) an encouraging rate of consent for DNA testing (including future testing) and relative contacting; 4) completed analyses of genetic linkage and association for several candidate gene markers and polymorphisms; 5) completed genotyping of random markers for over half of the full sample; and 6) early sharing of results among the four Family Blood Pressure Program networks for candidate and genome search analyses. CONCLUSIONS: Experience after four years of this five-year program (1995-2000) suggests that the newly initiated NHLBI Network Program mechanism is fulfilling many of the expectations for which it was designed. It may serve as a paradigm for future genetic research that can benefit from large sample sizes, frequent sharing of ideas among laboratories, and prompt independent confirmation of early findings, which are required in the search for common genes with relatively small effects such as those that predispose to human hypertension.

Adult↗

PubMed2000

The Family Risk Score for coronary heart disease: associations with lipids, lipoproteins, and body habitus in a middle-aged bi-racial cohort: The ARIC study.

PURPOSE: To examine the association between the Family Risk Score (FRS) for coronary heart disease (CHD) and body mass index (BMI), waist-to-hip ratio (WHR), high density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol, triglycerides, and lipoprotein(a) protein [Lp(a)]. METHODS: FRS was computed from observed and expected CHD events using family data collected from 11467 black and white adults of the Atherosclerosis Risk in Communities Study (ARIC). BMI, WHR, and lipids adjusted for study center, race, education, BMI (except BMI), WHR (except for BMI and WHR), cigarette smoking, alcohol, and Keys' score were compared among low (FRS < -0.5), average (-0.5 to 0.5), and high (> 0.5) FRS using analysis of covariance. The association between FRS and these risk factors was compared to that for simpler estimates of family risk. RESULTS: Adjusted means of BMI, WHR, LDL, LP(a), and triglycerides were positively associated with FRS, whereas HDL cholesterol was inversely associated with FRS. Of demographic and behavioral factors, cigarette smoking was most strongly associated with FRS. Based on additional comparisons of adjusted means, high vs. low levels of FRS appear to correlate better with CHD risk factors than do the simpler family history assessments. CONCLUSIONS: In situations were genetic or clinical information is not available, FRS may be a favorable measure of familial burden for CHD.

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

Familial risk of overweight and obesity in the Canadian population using the WHO/NIH criteria.

OBJECTIVE: To determine the familial risk of overweight and obesity in Canada. RESEARCH METHODS AND PROCEDURES: The sample was comprised of 15,245 participants from 6377 families of the Canada Fitness Survey. The risk of overweight and obesity among spouses and first-degree relatives of individuals classified as underweight, normal weight, pre-obese, or obese (Class I and II) according to the WHO/NIH guidelines for body mass index (BMI) was determined using standardized risk ratios. RESULTS: Spouses and first-degree relatives of underweight individuals have a lower risk of overweight and obesity than the general population. On the other hand, the risk of Class I and Class II obesity (BMI 35 to 39.9 kg/m2) in relatives of Class I obese (BMI 30 to 34.9 kg/m2) individuals was 1.84 (95% CI: 1.27, 2.37) and 1.97 (95% CI: 0.67, 3.25), respectively, in spouses, and 1.44 (95% CI:1.10, 1.78) and 2.05 (95% CI: 1.37, 2.73), respectively in first-degree relatives. Further, the risk of Class II obesity in spouses and first-degree relatives of Class II obese individuals was 2.59 (95% CI: -0.91, 6.09) and 7.07 (95% CI: 1.48, 12.66) times the general population risk, respectively. DISCUSSION: There is significant familial risk of overweight and obesity in the Canadian population using the BMI as an indicator. Comparison of risks among spouses and first-degree relatives suggests that genetic factors may play a role in obesity at more extreme levels (Class II obese) more so than in moderate obesity.

Adolescent↗