Biomedical subjects

T Rankinen

Publications and source records attributed to T Rankinen.

At least 37 records · Page 2Linked to original sources

PubMed2002

A 12-year follow-up study of treated obese children in Japan.

OBJECTIVE: To assess tracking for body weight from childhood to adulthood in obese Japanese children who were treated for obesity, investigate the relation between the changes in body weight status and morbidity, and identify correlates of the changes in body weight status. STUDY DESIGN: Twelve-year retrospective cohort study. SUBJECTS: A sample of 276 subjects (age 23.9+/-4.1, 176 males and 100 females) who responded to a questionnaire mailed in 1998 to 1047 children (age 10.6+/-2.2) treated for obesity at Mie National Hospital in Japan between 1976 and 1992. MEASUREMENTS: Based on height and weight from medical records during childhood, the relative weight (RW; weight expressed as a percentage of the standard body weight for age, height, and sex) was calculated. Degrees of childhood obesity were based on RW: slight obesity (120% < or = RW<130%; n=17), moderate obesity (130% < or = RW <150%; n=131), and severe obesity (RW > or = 150%; n=128). Adult body mass index (BMI), which was obtained from the mailed questionnaires, was classified as normal, overweight and obese according to the WHO/NIH criteria. Body weight tracking by degree of obesity was evaluated. Subjects with severe obesity during childhood (n=128) were examined for their weight status in adulthood, prevalence of chronic diseases in adulthood, and factors such as parental obesity, dietary and exercise habits and obesity treatment during childhood. RESULTS: Childhood obesity tracked into adulthood obesity or overweight in 54.7% of all cases. Severely obese children (36.7%) were more likely to be obese as an adult than moderately obese children (16.8%). The prevalence of adult obesity tended to be greater in boys with moderate childhood obesity than in girls (29.7% in boys vs 14.9% in girls, P=0.058). Among the severely obese children who became normal-weight adults, the prevalence of chronic diseases was about one-fifth of those who remained obese in adulthood (P=0.041). Four factors were associated with changes in body weight status: maternal BMI at entry (P=0.044), the changes in dietary and exercise habits after treatment (P=0.014, P=0.030, respectively), and satisfaction with obesity treatment in childhood (P=0.035). CONCLUSIONS: Severely obese children have a higher risk of becoming obese adults even when they received obesity treatment in childhood. The risk of adulthood obesity was twice as high in moderately obese boys than in girls. On the other hand, many cases of childhood obesity can be corrected with obesity treatment, which in turn can decrease the risk for adult chronic diseases.

Adolescent↗

PubMed2002

The effect of sex, age and race on estimating percentage body fat from body mass index: The Heritage Family Study.

OBJECTIVE: To study the effects of sex, age and race on the relation between body mass index (BMI) and measured percent body fat (%fat). DESIGN: Cross-sectional validation study of sedentary individuals. SUBJECTS: The Heritage Family Study cohort of 665 black and white men and women who ranged in age from 17 to 65 y. MEASUREMENTS: Body density determined from hydrostatic weighing. Percentage body fat determined with gender and race-specific, two-compartment models. BMI determined from height and weight, and sex and race in dummy coded form. RESULTS: Polynomial regression showed that the relationship between %fat and BMI was quadratic for both men and women. A natural log transformation of BMI adjusted for the non-linearity. Test for homogeneity of log transformed BMI and gender showed that the male-female slopes were within random variance, but the intercepts differed. For the same BMI, the %fat of females was 10.4% higher than that of males. General linear models analysis of the women's data showed that age, race and race-by-BMI interaction were independently related to %fat. The same analysis applied to the men's data showed that %fat was not just a function of BMI, but also age and age-by-BMI interaction. Multiple regression analyses provided models that defined the bias. CONCLUSIONS: These data and results published in the literature show that BMI and %fat relationship are not independent of age and gender. These data showed a race effect for women, but not men. The failure to adjust for these sources of bias resulted in substantial differences in the proportion of subjects defined as obese by measured %fat.

Adipose Tissue↗

PubMed2002

Genetics and blood pressure response to exercise, and its interactions with adiposity.

Regular aerobic exercise has the potential to induce several beneficial health effects, including a decrease in blood pressure level, especially in hypertensive patients and in subjects with high-normal blood pressure. However, it is also well documented that some people show more pronounced blood pressure responses to endurance training than others, despite identical training programs and similar initial blood pressure levels. This kind of variation is an example of normal biologic diversity and most likely originates from interactions with genetic factors. Data from genetic epidemiologic studies indicate that there is a genetic component that affects both resting blood pressure and blood pressure responses to acute exercise. Evidence from molecular genetic studies is scarce, but the first reports suggest that DNA sequence variation in the hypertension candidate genes, such as angiotensinogen, also modify blood pressure responses to endurance training. The current knowledge regarding the role of genetic factors in the modification of blood pressure responses to endurance training will be summarized and discussed.

Adipose Tissue↗

PubMed2001

Familial resemblance for glucose and insulin metabolism indices derived from an intravenous glucose tolerance test in Blacks and Whites of the HERITAGE Family Study.

Type 2 diabetes mellitus (T2DM), characterized by hyperglycemia, is a complex disease primarily caused by impairment in insulin sensitivity (SI) and insulin secretion. While a strong genetic component for T2DM is well established, there are few reports on racial differences in the magnitude of the genetic effects of T2DM and indices of glucose and insulin metabolism. We report here on the familial resemblance for traits related to glucose metabolism at pre-exercise training levels in 492 members from 99 sedentary White families and 259 members from 108 Black families participating in the multicenter HERITAGE Family Study. All these traits were obtained from the frequently sampled intravenous glucose tolerance test (IVGTT). They include glucose disappearance index (Kg), an overall index for glucose tolerance, acute insulin response to glucose (AIR(Glucose)) which is an index for insulin secretion, and those derived from the minimal model including SI and the disposition index (DI). DI, derived as the product of SI and AIR(Glucose), is a measure of the activity of the B-cells adjusted for insulin resistance. After adjustment for age, sex, and body mass index, the maximal heritability estimates in Blacks (Whites) are 48+/-14% (25+/-8%) for Kg, 44+/-14% (46+/-8%) for AIR(Glucose), 38+/-12% (44+/-8%) for SI and 32+/-14% (24+/-8%) for DI. Interestingly, Blacks have higher heritability for overall glucose tolerance than Whites but there is no race difference in heritability estimates for insulin sensitivity or insulin secretion.

Adult↗

PubMed2001

The human obesity gene map: the 2000 update.

This report constitutes the seventh update of the human obesity gene map incorporating published results up to the end of October 2000. Evidence from the rodent and human obesity cases caused by single-gene mutations, Mendelian disorders exhibiting obesity as a clinical feature, quantitative trait loci uncovered in human genome-wide scans and in cross-breeding experiments in various animal models, and association and linkage studies with candidate genes and other markers are reviewed. Forty-seven human cases of obesity caused by single-gene mutations in six different genes have been reported in the literature to date. Twenty-four Mendelian disorders exhibiting obesity as one of their clinical manifestations have now been mapped. The number of different quantitative trait loci reported from animal models currently reaches 115. Attempts to relate DNA sequence variation in specific genes to obesity phenotypes continue to grow, with 130 studies reporting positive associations with 48 candidate genes. Finally, 59 loci have been linked to obesity indicators in genomic scans and other linkage study designs. The obesity gene map reveals that putative loci affecting obesity-related phenotypes can be found on all chromosomes except chromosome Y. A total of 54 new loci have been added to the map in the past 12 months and the number of genes, markers, and chromosomal regions that have been associated or linked with human obesity phenotypes is now above 250. Likewise, the number of negative studies, which are only partially reviewed here, is also on the rise.

Animals↗

PubMed2001

The Trp64Arg polymorphism of the beta3-adrenergic receptor gene is not associated with training-induced changes in body composition: The HERITAGE Family Study.

OBJECTIVE: To investigate the association between the Trp64Arg polymorphism of the beta3-adrenergic receptor gene and changes in body composition in response to endurance training. RESEARCH METHODS AND PROCEDURES: Adult sedentary white and black subjects participating in the HERITAGE Family Study were measured before and after 20 weeks on endurance training for the body mass index, fat mass, percentage of body fat, fat-free mass, sum of eight skinfolds, and subcutaneous, visceral, and total abdominal fat areas. The association between the Trp64Arg polymorphism and the response phenotypes, computed as the difference between pre- and post-training values, was tested by analysis of covariance separately in men and women. The gene by race interaction term was also tested. RESULTS: No race differences were observed for allelic and genotype frequencies. Training resulted in significant reduction of body fat in both men and women. No association of the Trp64Arg polymorphism was observed with training-induced changes for any of the body composition phenotypes in both men and women. DISCUSSION: These results suggest that the Trp64Arg polymorphism of the beta3-adrenergic receptor gene is not related to changes in body composition in response to exercise training.

Adipose Tissue↗

PubMed2001

Polymorphisms in the leptin receptor gene, body composition and fat distribution in overweight and obese women.

OBJECTIVE: Leptin is an adipocyte-secreted hormone involved in body weight regulation, acting through the leptin receptor, localised centrally in the hypothalamus as well as peripherally, amongst others on adipose tissue. The aim of this study was to evaluate whether polymorphisms in the leptin receptor (LEPR) gene were related to obesity and body fat distribution phenotypes, such as waist and hip circumferences and the amount of visceral and subcutaneous fat. METHODS: Three known LEPR polymorphisms, Lys109Arg, Gln223Arg and Lys656Asn, were typed on genomic DNA of 280 overweight and obese women (body mass index (BMI)>25), aged 18-60 y. General linear model (GLM) analyses were performed in 198 pre- and 82 postmenopausal women, adjusting the data for age and menopausal state, plus fat mass for the fat distribution phenotypes. RESULTS: No associations were found between the LEPR polymorphisms and BMI or fat mass. In postmenopausal women, carriers of the Asn656 allele had increased hip circumference (P=0.03), total abdominal fat (P=0.03) and subcutaneous fat (P=0.04) measured by CT scan. Total abdominal fat was also higher in Gln223Gln homozygotes (P=0.04). Also in postmenopausal women, leptin levels were higher in Lys109Lys homozygotes (P=0.02). CONCLUSION: In conclusion, polymorphisms in the leptin receptor gene are associated with levels of abdominal fat in postmenopausal overweight women. Since body fat distribution variables were adjusted for fat mass, these results suggest that DNA sequence variations in the leptin receptor gene play a role in fat topography and may be involved in the predisposition to abdominal obesity.

Adipose Tissue↗

PubMed2001

Polymorphism in exon 6 of the dopamine D(2) receptor gene (DRD2) is associated with elevated blood pressure and personality disorders in men.

A deficient dopamine D(2) receptor (DA2) formation or action may contribute to hypertension via an increase of catecholamine release. In addition, Axis II personality disorders that appears odd or eccentric (cluster A) is associated with a low density of DA2. This study sought to examine if a NcoI restriction fragment length polymorphism (C to T transition) in exon 6 of the dopamine D(2) receptor gene (DRD2) was associated with these characteristics. The genotypes (CC, CT and TT) were compared in anthropometric, endocrine, metabolic and haemodynamic variables as well as estimates of personality disorders in 284 randomly selected 51-year-old men. Homozygotes for the C allele constituted 49% of the men and homozygotes for the T allele 9%, while heterozygotes were 41%. The TT genotype was associated with elevated systolic and diastolic blood pressure, independent of obesity and endocrine abnormalities, including the hypothalamic-pituitary-adrenal axis regulation. Moreover, the TT genotype was significantly more frequent among subjects with grade 1 (mild) hypertension (>140/90 mm Hg) compared to normotensive subjects (<130/85 mm Hg). The polymorphism in exon 6 of the DRD2 was also significantly associated with cluster A personality disorders. These results suggest that a polymorphism in exon 6 of the DRD2examined with the restriction enzyme NcoI is associated with an elevated blood pressure, independent of obesity. Paranoid or schizoid personality disorders is also associated with a polymorphism of the DRD2, which might be associated with a previously demonstrated low density of this receptor.

Alleles↗

PubMed2001

Changes in blood lipids consequent to aerobic exercise training related to changes in body fatness and aerobic fitness.

The contribution of changes in body fatness and aerobic fitness to changes in blood lipids after aerobic exercise training was investigated. The sample included 295 men (77 black, 218 white) and 355 women (131 black, 224 white), aged 17 to 65 years, from the HERITAGE Family Study. Participants underwent measurements at baseline and after 20 weeks of supervised exercise training on a cycle ergometer. Body fat mass (FM, in kilograms) was determined by underwater weighing, and aerobic fitness (maximal oxygen uptake, VO(2max), in milliliters per minute) was assessed by cycle ergometry. Blood lipid measurements included fasting plasma levels of high-density lipoprotein cholesterol (HDL-C), HDL(2)-C, HDL(3)-C, low-density lipoprotein cholesterol (LDL-C), total cholesterol (CHOL), CHOL/HDL, and triglycerides (TG). A composite lipid change index (LCI) was derived by subjecting the Delta scores for the individual blood lipids to principal components analysis. The exercise training was accompanied by a mean increase of 17.5% in VO(2max) and a mean decrease of 3.3% in FM. Partial correlations, controlled for age, between absolute changes in VO(2max) and changes in the blood lipids were consistently low and nonsignificant. On the other hand, absolute changes in FM were significantly (P <.05) associated with changes in HDL-C (r = -.23), HDL(2)-C (r = -.17), and CHOL/HDL (r =.24) and the LCI (r = -.27) in men and with changes in LDL-C (r =.22), CHOL (r =.19), and CHOL/HDL (r =.15) and the LCI (r = -.19) in women. Forward stepwise regression confirmed that the change in FM was a better predictor of changes in blood lipids than the change in VO(2max), entering as a predictor in 4 of 8 regressions in both men and women. Change in VO(2max) did not enter as a significant predictor in any regression. Further, there were no differences in LCI between the upper and lower quartiles of VO(2max) change. On the other hand, there were significant differences between the low and high quartiles of FM change. No race effects were observed in any of the relationships, except that race was a significant predictor of changes in TG in both men and women. In conclusion, changes in blood lipids associated with aerobic exercise training do not appear to be related to changes in aerobic fitness per se; rather, they are weakly to moderately associated with changes in body fatness.

Adipose Tissue↗

PubMed2001

Relationship of changes in maximal and submaximal aerobic fitness to changes in cardiovascular disease and non-insulin-dependent diabetes mellitus risk factors with endurance training: the HERITAGE Family Study.

The purpose of this study was to determine the relationship between changes in maximal oxygen uptake (VO2 max) and submaximal markers of aerobic fitness and changes in risk factors for cardiovascular disease (CVD) and non-insulin-dependent diabetes mellitus (NIDDM) consequent to a 20-week endurance training program. The 502 participants in this study were healthy and previously sedentary men (n = 250) and women (n = 252) of varying age (17 to 65 years) and race (blacks n = 142; whites n = 360) who had completed the HERITAGE Family Study testing and training protocol. Following baseline measurements, participants trained on cycle ergometers 3 days/week for a total of 60 exercise sessions starting at the heart rate (HR) associated with 55% of VO2 max for 30 minutes/session. This was progressively increased to the HR associated with 75% of VO2 max for 50 minutes/session, which was maintained during the last 6 weeks. VO2 max, heart rate at 50 W, power output at 60% of VO2 max, lipids and lipoproteins, resting blood pressure, body composition including abdominal fat (computed tomography [CT] scan), and blood glucose and insulin at rest and at peak following an intravenous glucose tolerance test (IVGTT) were determined both before and after training. Following training, there were significant increases in VO2 max (16%) and the power output at 60% of VO2 max and a significant decrease in HR at 50 W. These changes in markers of aerobic fitness were significantly correlated only to the changes in the body composition variables and the lipids and lipoproteins. Further, there was considerable individual variation in response for all variables studied. Finally, when risk factor data were analyzed by quartile of change in VO2 max, there were few significant relationships. It is concluded that there is a significant relationship between changes in markers of aerobic fitness and changes in several risk factors for CVD and NIDDM. However, the magnitude of these relationships is small.

Adolescent↗

PubMed2001

Genome-wide linkage scan to detect loci influencing levels of dehydroepiandrosterones in the HERITAGE Family Study.

A genome-wide linkage scan was performed to identify genomic regions that influence levels of dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), and DHEA fatty acid esters (DHEA-FA) at baseline and in response to 20 weeks of endurance exercise training in sedentary white and black participants in the HERITAGE Family Study. The baseline levels were log-transformed and adjusted for the effects of age and sex prior to genetic analysis. The training responses were adjusted for the effects of age, sex, and the baseline values. A total of 509 autosomal component polymorphic markers were used for the genome scan with an average spacing of 6.0 Mb. Multipoint variance components linkage analyses were performed in nuclear families containing 360 white and 106 black sibling pairs. We found 5 genomic regions with significant linkages for baseline DHEA-FA in whites, with log odd (LOD) scores over 3.6 (P < 2 x 10(-5)). They include (1) D1S468 (LOD 4.56, 2.533 Mb, 1p36.22); (2) D2S177 (LOD 5.65, 52.663 Mb, 2p16.3); (3) D4S2397 (LOD 3.98, 32.246 Mb, 4p15.2); (4) the paraoxonase loci (LOD 3.93 approximately 3.99, 101.544 approximately 102.933 Mb, 7q21.3), and D7S821 (LOD 3.88, 104.497 Mb, 7q22.1); and (5) D12S372 (LOD 4.66, 2.129 Mb, 12q13.33). In addition, we obtained evidence of suggestive linkages (2.2 < LOD < 3.6; 2 x 10(-5) < P < 7 x 10(-4)) on chromosomes 3p, 6q, and 8q for baseline DHEAS; on chromosomes 2q, 3p, 9q, 10p, 16q, and 17p for baseline DHEA-FA in whites; and on chromosomes 9q and 11p for baseline DHEA in blacks. This is the first genome-wide linkage scan searching for genomic regions influencing human DHEA levels. Several potential candidate genes are located in these genomic regions, which warrant further studies in HERITAGE and other cohorts.

Adult↗

PubMed2001

The human gene map for performance and health-related fitness phenotypes.

The aim of this paper is to describe the first human gene map for physical performance and health-related fitness traits based on the papers published until the end of 2000. Studies of candidate genes using case-control and other designs are reviewed. Quantitative trait loci from the limited evidence reported to date in genomic scans are also incorporated. Performance and fitness phenotypes in the sedentary state as well as their changes during exercise, if applicable, or in response to exercise training are considered. Physical performance traits include cardiorespiratory endurance indicators and muscular strength or muscular performance variables. Health-related fitness phenotypes are grouped under the following categories: hemodynamic traits; anthropometry and body composition; insulin and glucose metabolism; and lipids, lipoproteins, and hemostatic factors. A yearly update of this human gene map will be published.

Anthropometry↗

PubMed2001

Individual differences in response to regular physical activity.

PURPOSE: The purpose of this review was to address the question of interindividual variation in responsiveness to regular exercise training and to define the contributions of age, sex, race, and pretraining phenotype level to this variability. METHODS: A literature review was conducted of the studies reporting interindividual variation in responsiveness to standardized and controlled exercise-training programs, and included an analysis of the contribution of age, sex, race, and initial phenotype values to the heterogeneity in VO(2max), high-density lipoprotein (HDL)-C and submaximal exercise, heart rate (HR), and systolic blood pressure (SBP) training responses in subjects from the HERITAGE Family Study. RESULTS: Several studies have shown marked individual differences in responsiveness to exercise training. For example, VO(2max) responses to standardized training programs have ranged from almost no gain up to 100% increase in large groups of sedentary individuals. A similar pattern of heterogeneity has been observed for other phenotypes. Data from the HERITAGE Family Study show that age, sex, and race have little impact on interindividual differences in training responses. On the other hand, the initial level of a phenotype is a major determinant of training response for some traits, such as submaximal exercise heart rate and blood pressure (BP) but has only a minor effect on others (e.g., VO(2max), HDL-C). The contribution of familial factors (shared environment and genetic factors) is supported by data on significant familial aggregation of training response phenotypes. CONCLUSIONS: There is strong evidence for considerable heterogeneity in the responsiveness to regular physical activity. Age, sex, and ethnic origin are not major determinants of human responses to regular physical activity, whereas the pretraining level of a phenotype has a considerable impact in some cases. Familial factors also contribute significantly to variability in training response.

Adult↗

PubMed2001

Angiogenin gene-race interaction for resting and exercise BP phenotypes: the HERITAGE Family Study.

We examined the association between an angiogenin gene polymorphism and blood pressure (BP) at rest and in response to acute exercise before and after a 20-wk endurance-training program. Subjects were 737 normotensive and borderline hypertensive subjects (257 black and 480 white). The polymorphism was detected by PCR and digestion with AvaII, yielding an allele of 253 bp or a rare allele of 194 + 59 bp. Resting and exercise [50 W; 60, 80, and 100% of maximal O2 consumption (VO2 max)] systolic (SBP) and diastolic BP were determined before and after training. Among blacks, adjusted SBP in the sedentary state was significantly lower in carriers of the rare allele at rest and exercise intensities of 60, 80, and 100% of VO2 max. In the trained state, carriers of the rare allele had a significantly (P < 0.05) lower SBP than did noncarriers at rest and at 80 and 100% of VO2 max. The genotypic effect observed among blacks was not evident among whites. Furthermore, change in BP (after--before) was not significantly associated with the genotype. In conclusion, the angiogenin gene AvaII polymorphism is associated with a lower SBP at rest and in response to acute high-intensity exercise in blacks but not in whites.

Adult↗

PubMed2001

TGF-beta(1) gene-race interactions for resting and exercise blood pressure in the HERITAGE Family Study.

We examined the possible association between a transforming growth factor (TGF)-beta(1) gene polymorphism in codon 10 and blood pressure (BP) at rest, in acute response to exercise in the pretrained (sedentary) and trained states, as well as in its training response (Delta) to 20 wk of endurance exercise. Subjects were 257 black and 480 white, healthy sedentary normotensive subjects from the HERITAGE Family Study. The polymorphism was detected by polymerase chain reaction and digestion with the Msp A1 I endonuclease yielding a wild (leucine-10) and a mutant (proline-10) allele. Resting and exercise [50 W plus 60, 80, and 100% maximal oxygen consumption (VO(2)(max))] BP were determined before and after training. Significant (P < 0.05) race-genotype interactions were found for systolic (S) BP in both the sedentary and trained states. Among whites but not in blacks, the TGF-beta(1) genotypes were significantly (P < 0.05) associated with sedentary-state SBP at rest, at 50 W, and at 60 and 100% VO(2)(max)as well as with trained-state SBP at rest and at 80 and 100% VO(2)(max). The leucine-10 homozygotes had significantly (P < 0.05) lower SBP than proline-10 homozygotes. DeltaBP was not significantly associated with genotype. These results support the hypothesis of an association between the TGF-beta(1) marker in codon 10 and SBP at rest and in response to acute exercise in whites but not in blacks.

Adult↗

PubMed2001

Genomic scan for exercise blood pressure in the Health, Risk Factors, Exercise Training and Genetics (HERITAGE) Family Study.

Agenome-wide linkage scan was performed for genes affecting submaximal exercise systolic blood pressure (SBP) and diastolic blood pressure (DBP) in the sedentary state and their responses to a standardized endurance training program. A total of 344 polymorphic markers were used, and 344 pairs of siblings from 99 white nuclear families and 102 sibling pairs from 105 black family units were available for the study. All subjects were healthy but sedentary at baseline. SBP and DBP were measured during exercise tests at 2 different intensities: 50 W (SBP50 and DBP50) and 80% of maximal oxygen consumption (SBP80 and DBP80). Baseline blood pressure phenotypes were adjusted for age, gender, and body mass index, and the training responses (after training minus baseline [Delta]) were adjusted for age, gender, baseline body mass index, and baseline blood pressure. Two analytical strategies were used: a multipoint variance-components linkage analysis using all the family data and a single-point linkage analysis using pairs of siblings. In whites, promising linkages (lod score >1.75) were detected for baseline SBP80 on 10q23-q24 and for DeltaSBP50 on 8q21. In addition, several chromosomal regions with suggestive evidence of linkage (lod score 1.0 to 1.75) were observed for SBP50 (22q11.2-q13), DBP50 (6q23-q27), SBP80 (2p24, 2q21, 14q11.1-q12, and 16q21), DBP80 (6q13-q21), DeltaSBP50 (7p12-p13), and DeltaDBP50 (5q31-q32). In blacks, DBP50, DBP80, and DeltaDBP80 showed promising quantitative trait loci on 18p11.2, 11q13-q21, and 10q21-q23, respectively. Suggestive linkages were evident for DBP50 on 2p22-p25, 11p15.5, and 18q21.1; for SBP80 on 6q21-q21, 6q31-q36, 12q12-q13, 15q12-q13, and 17q11-q12; and for DBP80 on 8q24, 10q21-q24, and 12p13. All the detected chromosomal regions include several potential candidate genes and therefore warrant further studies in the Health, Risk Factors, Exercise Training and Genetics (HERITAGE) cohort and other studies.

Blood Pressure↗

PubMed2001

Leptin receptor gene polymorphisms are associated with insulin in obese women with impaired glucose tolerance.

Leptin receptors are present on beta-cells as well as on muscle and fat cells, thus enabling leptin to modulate both insulin secretion and insulin action. Leptin inhibits especially the glucose-stimulated insulin secretion from pancreatic cells. The leptin receptor (LEPR) gene could thus play a role in the regulation of glucose and insulin after an oral glucose load. Therefore, the relationship between LEPR polymorphisms and glucose and insulin response to an oral glucose tolerance test (OGTT) was investigated. Three LEPR polymorphisms (Lys(109)Arg, Gln(223)Arg, and Lys(656)Asn) were typed on genomic DNA of 358 overweight and obese women, aged 18-60 yr. Based on an OGTT, 269 subjects were defined with normal glucose tolerance, and 89 with impaired glucose tolerance (IGT). Associations between genotypes and glucose metabolism were analyzed with a general linear models procedure in pre- and postmenopausal women separately, after adjusting the data for age and fat mass. In postmenopausal women with IGT (n = 24), associations were found with Lys(109)Arg and Lys(656)Asn for fasting insulin (P = 0.05) and with Lys(109)Arg and Gln(223)Arg for the insulin response to an OGTT (P < 0.02). In the same group, trends were found with Lys(656)Asn for fasting glucose as well as in response to the OGTT. In premenopausal women with IGT (n = 65), associations were found with Lys(109)Arg and Lys(656)Asn for overall glucose response to the glucose load. In contrast, no associations with insulin or glucose were found in women with normal glucose tolerance. In conclusion, these data indicate that LEPR polymorphisms are associated with insulin and glucose metabolism in women with impaired glucose homeostasis.

Adolescent↗

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↗