Biomedical subjects

D C Rao

Publications and source records attributed to D C Rao.

At least 109 records · Page 6Linked to original sources

PubMed2002

The hormone-sensitive lipase gene and body composition: the HERITAGE Family Study.

OBJECTIVE: To investigate whether the C-60G polymorphism and other markers in the hormone-sensitive lipase (LIPE) gene are associated with baseline body composition and free-fatty acid (FFA) concentrations measured at rest and during low-intensity exercise in white and black subjects participating in the HERITAGE Family Study. SUBJECTS: Adult sedentary white (245 men and 258 women) and black (91 men and 185 women) subjects. MEASUREMENTS: body mass index (BMI); fat mass (FAT); percentage body fat (%FAT); fat-free mass (FATFR); sum of eight skinfolds (SF8); subcutaneous (ASF), visceral (AVF) and total (ATF) abdominal fat areas assessed by CT scan; plasma FFA concentrations measured at rest (FFAR), at a power output of 50 W (FFA50) and at a relative power output of 60% of VO(2max) (FFA60%); and fasting insulin (INS). STATISTICAL ANALYSIS: Association between the C-60G polymorphism of the LIPE gene and each phenotype was tested separately in men and women using ANCOVA with the effects of age and race as covariates and with further adjustment for FAT for ASF, AVF, ATF, FFAR, FFA50 and FFA60%. Secondly, owing to significant gene-by-race interaction, associations were investigated separately in each of the two race groups. Linkage was tested with the C-60G polymorphism, a dinucleotide repeat polymorphism in the intron 7 of the LIPE gene and two microsatellites markers (D19S178 and D19S903) flanking the LIPE gene. RESULTS: There were no race differences in the allele frequencies of the C-60G polymorphism of the LIPE gene. No association or gene-by-race interaction was observed in men. However, in women, strong gene-by-race interactions were observed for BMI (P=0.0005), FAT (P=0.0007), %FAT (P=0.0003), SF8 (P=0.0001), ASF (P=0.03) and ATF (P=0.01). When the analysis was performed separately in each race, white women carriers of the -60G allele exhibited lower %FAT (P=0.005) and SF8 (P=0.01) than non-carriers, while in black women, the -60G allele was associated with higher BMI (P=0.004), FAT (P=0.009), %FAT (P=0.01) and SF8 (P=0.0009). These associations were no longer significant after adjusting for INS. Evidence of linkage was observed in whites with ATF, FFAR, FFA50 and FFA60%. CONCLUSION: These results suggest that the C-60G polymorphism in the LIPE gene plays a role in determining body composition and that its effect is sex-, race- and insulin-dependent.

Abdomen↗

PubMed2002

Is adiposity at normal body weight relevant for cardiovascular disease risk?

OBJECTIVE: To examine the relation between adiposity and risk factors for cardiovascular disease (CVD) in normal weight (NW) individuals. METHODS: Cross-sectional study using the sample of white people, aged from 17 to 60 y from the Québec Family Study and the Heritage Family Study. NW subjects with a body mass index (BMI) between 18.5 and 25 kg/m(2) (181 males and 265 females) and overweight (OW) subjects with a BMI between 25 and 30 kg/m(2) (133 males and 114 females) were retained for this study. NW subjects were divided into quintiles of each adiposity variable, then the quintiles and the OW group were evaluated for the presence of CVD risk factors. Using logistic regression analysis, the odds ratio (OR) for the prevalence of risk factors for each quintile of each adiposity variable and the OW group was estimated relative to the first quintile in NW subjects. Mean values of adiposity variables were compared between the subjects with and without risk factors. In these analyses, age and study cohort effects were taken into account. MEASUREMENTS: Percentage body fat (%fat) and fat mass (FM) measured by underwater weighing were available as adiposity variables. Risk factors included systolic and diastolic blood pressure, LDL and HDL cholesterol, triglycerides and fasting glucose. RESULTS: Wide ranges of values were observed for adiposity variables. HDL cholesterol, triglycerides and fasting glucose in NW males and HDL cholesterol in NW females were significantly correlated with all adiposity variables. For males, higher quintiles of adiposity variables in the NW group and the OW group tended to have higher ORs compared to the first quintiles for the risk factor variables. The fifth quintiles of all adiposity variables had the highest ORs (3.15 for %fat and 3.77 for FM) and they were significantly different from the first quintiles. OW males had ORs similar to those of the fifth quintiles for the risk factor variables. On the other hand, for females, the relatively linear associations were less clear in the NW group. In NW males, the subjects with at least one risk factor had significantly higher %fat and FM than the subjects without risk factors. In NW females, no significant difference was observed for these adiposity variables between the subjects with and without risk factors. CONCLUSION: NW males with elevated adiposity had higher prevalence of risk factors than NW males with less adiposity and the prevalence in the former was rather similar to that seen in OW males. On the other hand, measures of adiposity added little additional information to the BMI classification of NW on CVD risk factors in females.

Adipose Tissue↗

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

A genetic study of cortisol measured before and after endurance training: the HERITAGE Family Study.

The aim of this study was to investigate whether there are familial influences on cortisol levels at baseline and in response to endurance exercise training and, if so, whether there is evidence for a major gene effect. There were 476 white individuals in 99 nuclear families and 247 black individuals in 105 families with valid cortisol data in the HERITAGE Family Study. Data adjustments were carried out separately in each of 8 sex by generation by race groups, using stepwise multiple regression procedures. The familial factors underling the variability in baseline cortisol (log-transformed and adjusted for age and baseline body mass index [BMI]) and its training response (post-training minus baseline, adjusted for age, baseline BMI, and the baseline cortisol value) were assessed by estimating familial correlations and carrying out segregation analysis. In the white sample, significant familial resemblance was detected for both baseline cortisol and the training response, with maximal heritabilities of 38% and 32%, respectively. However, significant familial correlations were not detected for either cortisol phenotype in the black sample, perhaps owing, in part, to the much smaller family sizes. Results of segregation analysis of the white sample provided evidence for Mendelian additive genes influencing baseline cortisol and its training response. The major genes accounted for 33% and 31% of the variance for baseline cortisol and the training response with 48% and 5% of the sample homozygous for the genotype leading to high values, respectively. In conclusion, we found significant familial effects influencing levels of baseline cortisol and its training response in the white sample. The putative major gene effects appear to explain most of the observed familial resemblance, this will motivate further linkage and association studies.

Adolescent↗

PubMed2002

Variability in the response of HDL cholesterol to exercise training in the HERITAGE Family Study.

In the HERITAGE Family Study, 675 sedentary, healthy, white and black men and women, aged 17 to 65 years, performed 20 weeks of supervised cycle ergometer exercise at the same relative intensity and weekly volume. As a group, subjects had normal mean baseline lipid levels for North Americans with the exception of below average high density lipoprotein cholesterol (HDL-C) levels. A significant mean increase in plasma HDL-C of 3.6 % was observed; however, there was marked variability in responsiveness to training, ranging from a mean 9.3 % decrease in Quartile 1 of HDL-C response to a mean 18 % increase in Quartile 4 (P < 0.0001 by ANOVA). Parallel changes in HDL(2)-C and HDL(3)-C, apolipoprotein A-I levels, and lipoprotein lipase activity were noted across quartiles. The change in HDL-C across quartiles was inversely related to baseline HDL-C (p < 0.0001) and to changes with training in plasma triglycerides (p = 0.0007). No significant differences in HDL-C response were observed across quartiles by sex, race, age, or increase in VO(2)max with training; however, weak positive associations were observed with age-adjusted education level and with reduction in abdominal fat and increase in VO(2)max at the ventilatory threshold following training. Multivariate regression analysis including baseline variables and training responses only accounted for 15.5 % of the variability in the HDL-C response to training. Thus, marked variability was found in the HDL-C response to the same endurance exercise training stimulus with only a modest amount of the response predictable by identified nongenetic factors.

Adaptation, Physiological↗

PubMed2002

Associations between angiotensinogen gene variants and left ventricular mass and function in the HyperGEN study.

BACKGROUND: The angiotensinogen M235T polymorphism is positively associated with plasma angiotensinogen, hypertension, and coronary heart disease. However, the association of M235T polymorphism with left ventricular (LV) mass and function is not well defined at the population level. We investigated whether 2 tightly linked polymorphisms of angiotensinogen gene, M235T and G-6A, are associated with LV mass and function in a large population-based sample, composed mostly of patients with hypertension. METHODS: Two-dimensional guided M-mode and pulsed Doppler scan echocardiograms were performed in 605 participants. The angiotensinogen M235T was analyzed with a standard polymerase chain reaction test, and the G-6A variant was measured with mass spectrophotometry. RESULTS: The association of angiotensinogen gene to LV mass and LV mass indexed to body surface area (LVMI) differed significantly between subjects with normotensive and hypertensive conditions with respect to the direction of association (P <.005). The methionine-threonine/threonine-threonine genotype was negatively associated with LV mass and LVMI in patients with hypertension after adjustment for blood pressure, antihypertensive medication use, weight, and other covariates (P <.001), and patients with normotensive conditions with the methionine-threonine/threonine-threonine genotype had higher LV mass and LVMI (P =.04, for LV mass; P =.14, for LVMI). The association in patients with normotensive conditions was not influenced by blood pressure but was partly confounded by weight. CONCLUSION: Variation in the angiotensinogen gene was modestly associated with LV mass independently of covariates in patients with hypertensive conditions. The direction of the association was opposite to that observed in patients with normotensive conditions, probably because of the influence of other risk factors or antihypertensive medication use or both.

Analysis of Variance↗

PubMed2002

Considerations on study designs using the extreme sibpairs methods under multilocus oligogenic models.

Several issues pertinent to study designs employing extreme sibpairs (ESP) methods to detect complex oligogenic quantitative trait loci (QTL) are investigated in the setting of genome-wide multipoint scans. We demonstrate that when stringent alpha-levels are imposed (e.g., alpha = 0.00022 as recommended by Landers and Kruglyak), the power to detect a susceptibility locus could drop from 83.6% under a one-locus model down to a hopeless 22.8% under a two-locus model of the same heritability h(2) = 0.5 and gene frequency (p = 0.1). We introduce the notion of joint power that is the power to detect linkage to at least one location over a given panel of markers across a genomic region and describe the effect of several design factors on such joint power in a multipoint scan. Moreover, power of analysis conditional on the IBD sharings of ESPs at a known/detected locus is examined and shown to increase substantively (to 93.3% under the previous two-locus model) in detecting novel trait loci. We conclude that with such remedies, the ESP design continues to be a relatively powerful design for mapping oligogenic QTL. However, when the effect of individual contributing loci becomes less tractable, especially when their contributions are "asymmetric," deliberation on balancing two types of statistical errors and a careful examination of possible contributions from multiple genetic factors and/or interaction effects are a must in designing an efficient study.

Genotype↗

PubMed2002

Menopause, estrogen, and training effects on exercise hemodynamics: the HERITAGE study.

PURPOSE: To investigate the influences of menopause, hormone replacement, and endurance exercise training on cardiovascular hemodynamics and oxygen uptake parameters during exercise in women. METHODS: Subjects were 338 premenopausal women, 29 postmenopausal women taking hormone replacement, and 28 postmenopausal women not taking hormone replacement, all enrolled in the HERITAGE Family Study. Hemodynamic and oxygen uptake data were gathered on a cycle ergometer at 50 watts (W), 60% peak oxygen uptake, and at peak exercise, both before and after a 20-wk regimen of endurance exercise training on a cycle ergometer. RESULTS: Systolic blood pressure (SBP) during peak exercise was found to be an average of 14 mm Hg less in postmenopausal women receiving hormones than in those not receiving hormones. Furthermore, menopause was associated with a 26.2 mm Hg higher SBP at 50 W power output, which remained physiologically significant after adjustment for age. At 50 W, postmenopausal women not taking hormones showed a 13.8 mm Hg greater training-induced reduction in SBP than those taking hormones. CONCLUSION: It was concluded that hormone replacement may be associated with a vasodilatory reserve at high exercise intensities and that endurance exercise training elicits favorable hemodynamic and oxygen uptake adaptations during exercise that are, in most instances, independent of menstrual status or hormone replacement.

Adaptation, Physiological↗

PubMed2002

Heritability of HR and BP response to exercise training in the HERITAGE Family Study.

PURPOSE: The heritability of the response to exercise training in resting blood pressure (BP) and heart rate (HR) was assessed in 482 Caucasian individuals comprising 98 families participating in the HERITAGE Family Study. METHODS: All individuals were sedentary at the baseline visit (time 1 measurement). After completing a 20-wk exercise-training program, subjects were measured again (time 2). A familial correlation model was used to assess the heritability (genetic plus familial environmental) of the response in resting systolic BP (SBP), diastolic BP (DBP), and HR, computed as the difference between the two measurement times. This response was adjusted for the effects of baseline levels and age within sex and generation groups. Analyses were conducted separately in a subsample of families in which at least one family member was considered to have elevated BP (95th percentile; SBP > or = 135 or DBP > or = 80). RESULTS: Several novel findings emerged from this study. First, the SBP and HR response may be influenced by genetic factors. The maximal heritabilities were 20% (SBP) and 36% (HR) in the elevated BP, 18% and 24% in the complete, and not significant in the normotensive samples. For DBP, there were cohort effects (significant sibling and spouse but not parent-offspring correlations) in the complete and normotensive samples that may be due to generation-specific environmental influences. CONCLUSION: The trainability of SBP and HR in families with elevated BP appears to be determined in part by genetic factors, whereas DBP trainability may be more a function of environmental effects.

Adolescent↗

PubMed2002

Familial aggregation of physical activity levels in the Québec Family Study.

PURPOSE: Familial aggregation of physical activity phenotypes was investigated in 696 subjects from 200 families of the Quebec Family Study. The mean age of offspring and parents was 27 and 53 yr, respectively. METHODS: The levels of physical activity were estimated using a 3-d diary and a questionnaire dealing with physical activity during the past year. RESULTS: An ANOVA performed on the age and sex adjusted physical activity phenotypes revealed that there were 1.40-1.52 times more variation in physical activity levels between families than within families (0.001 < P < 0.0001), suggesting that physical activity levels aggregate in families. Maximal heritabilities (SEGPATH), adjusted for the degree of spouse resemblance, reached 25%, 16%, 19%, and 17% for the degree of inactivity, time spent in moderate to strenuous physical activities, total level of daily activity, and weekly time spent in the main activity during the previous year, respectively. CONCLUSION: These results suggest that physical activity level is characterized by a significant degree of familial resemblance, and that inactivity has a slightly higher heritability level than moderate to strenuous physical activity or total physical activity phenotypes. The pattern of familial correlations suggests that shared familial environmental factors along with genetic factors are also important in accounting for the familial resemblance in physical activity level.

Adolescent↗

PubMed2002

Major gene effects on exercise ventilatory threshold: the HERITAGE Family Study.

This study investigates whether there are major gene effects on oxygen uptake at the ventilatory threshold (VO(2VT)) and the VO(2VT) maximal oxygen uptake (VT%VO(2 max)), at baseline and in response to 20 wk of exercise training by using data on 336 whites and 160 blacks. Segregation analysis was performed on the residuals of VO(2VT) and VT%VO(2 max). In whites, there was strong evidence of a major gene, with 3 and 2% of the sample in the upper distribution, that accounted for 52 and 43% of the variance in baseline VO(2VT) and VT%VO(2 max), respectively. There were no genotype-specific covariate effects (sex, age, weight, fat mass, and fat-free mass). The segregation results were inconclusive for the training response in whites, and for the baseline and training response in blacks, probably due to insufficient power because of reduced sample sizes or smaller gene effect or both. The strength of the genetic evidence for VO(2VT) and VT%VO(2 max) suggests that these traits should be further investigated for potential relations with specific candidate genes, if they can be identified, and explored through a genome-wide scan.

Aging↗

PubMed2002

Uncoupling protein 3 gene is associated with body composition changes with training in HERITAGE study.

The uncoupling protein 3 (UCP3) is a mitochondrial membrane transporter mainly expressed in skeletal muscle that we have shown to be associated with obesity. We have analyzed UCP3 polymorphisms, Val102Ile, Tyr210Tyr, and a new microsatellite GAIVS6 located in the sixth intron, among 276 black and 503 white subjects from the HERITAGE Family Study. Linkage and association studies were undertaken with body composition variables measured in a sedentary state (baseline) and after 20 wk of endurance training (changes). Allele and genotype frequencies were found to be significantly different between whites and blacks. Suggestive linkages (0.009 < or = P < or = 0.033) with Tyr210Tyr were found in blacks and whites for baseline body mass index, fat mass, or leptin level and with GAIVS6 in whites for changes in fat mass and percent body fat. Associations were also found in whites between GAIVS6 and changes in the sum of eight skinfold thicknesses (P = 0.0006), with a borderline result for body mass index (P = 0.06). We concluded that UCP3 could be involved in body composition changes after regular exercise.

Adult↗

PubMed2002

A polymorphism in the human agouti-related protein is associated with late-onset obesity.

The mouse agouti-related protein (AGRP) is a powerful appetite effector that results in hyperphagia and the development of obesity when administered intracerebroventricularly or when overexpressed in transgenic mice. Animal studies have also shown that exogenous administration of AGRP predisposes toward hedonic intake of high fat and high sucrose diets. The human ortholog (hAGRP) maps on chromosome 16q22 and has similar physiological properties, as tested in animal models. A polymorphism was identified in the third exon of hAGRP, c.199G-->A, that resulted in a nonconservative amino acid substitution, Ala(67)Thr. Computational analysis of the protein showed significant differences in the coils of the two polymorphic isoforms of the protein. Human studies showed no genotype effects in individuals with a mean age of 25 yr. However, the G/G genotype was significantly associated with fatness and abdominal adiposity in the parental population with a mean age of 53 yr. The c.199G-->A polymorphism in hAGRP could, therefore, play a role in the development of human obesity in an age-dependent fashion.

Adenine↗

PubMed2002

Melanocortin 4 receptor sequence variations are seldom a cause of human obesity: the Swedish Obese Subjects, the HERITAGE Family Study, and a Memphis cohort.

The prevalence of mutations within and in the flanking regions of the gene encoding the melanocortin 4 receptor was investigated in severely obese and normal-weight subjects from the Swedish Obese Subjects study, the Health, Risk Factors, Exercise Training, and Genetics (HERITAGE) Family study, and a Memphis cohort. A total of 433 white and 95 black subjects (94% females) were screened for mutations by direct sequencing. Three previously described missense variants and nine novel (three missense, six silent) variants were detected. None of them showed significant association with obesity or related phenotypes. In addition, two novel deletions were found in two heterozygous obese women: a -65_-64delTG mutation within the 5' noncoding region and a 171delC frameshift mutation predicted to result in a truncated nonfunctional receptor. No pathogenic mutations were found among obese blacks or nonobese controls. Furthermore, none of the null mutations found in other populations was present in this sample. In conclusion, our results do not support the prevailing notion that sequence variation in the melanocortin 4 receptor gene is a frequent cause of human obesity.

5' Untranslated Regions↗

PubMed2002

A genome-wide linkage scan for steroids and SHBG levels in black and white families: the HERITAGE Family Study.

To identify loci-harboring genes affecting steroid hormone and SHBG plasma levels, a genomic-wide scan was performed in the HERITAGE Family Study at baseline. The following steroid hormones were assayed: androstane-3 alpha, 17 beta-diol glucuronide, androsterone glucuronide, cortisol, dihydrotestosterone, estradiol, 17-hydroxyprogesterone (OH-PROG), progesterone (PROG), pregnenolone ester, and testosterone. A total of 509 markers on the 22 autosomes were genotyped, and a maximum of 357 pairs of siblings from white families and 103 from black families were available for the study. Significant linkages with LOD scores over 3.6 (P < 2.2 x 10(-5)) for SHBG were observed in blacks on 1q44 (D1S321), 5p13.3 (D5S1986), 10q24.1 (D10S1239), and 12q12 (D12S1653) in both singlepoint and multipoint analyses. Promising evidence of linkage (1.75 < LOD < 3.6; 2.2 x 10(-5) < P < 0.0023) for SHBG was observed on 1q44 in singlepoint analysis in whites. In addition, several other loci in blacks exhibited promising evidence of linkage, suggesting that many genes can potentially regulate SHBG levels. In the case of C21 steroids, promising linkages were found on 1q43 (D1S517) for PROG, 2p25.1 (D2S1400) for pregnenolone ester, and 18q21.32 (D18S38) for OH-PROG in whites and on 3q25.33 (D3S1763) for OH-PROG in blacks, both singlepoint and multipoint analyses (P < 0.0023). The strongest signals for C19 steroids were found on 22q12.3 for testosterone in whites (P = 0.0024 in multipoint) and on 8q22.1 for dihydrotestosterone in blacks. In blacks, the strongest evidence of linkage for estradiol (C18 steroid) was provided by marker D1S1588 on 1p21.3 and in whites by markers D2S2374 and D2S2347 on 2p21, and D6S465 on 6p12.3. Several genes encoding enzymes of the steroid biosynthesis pathways but also other potential candidate genes were located in the vicinity of the genomic regions showing evidence of linkage in this genomic scan.

17-alpha-Hydroxyprogesterone↗

PubMed2002

A genomewide linkage scan for abdominal subcutaneous and visceral fat in black and white families: The HERITAGE Family Study.

Abdominal visceral fat (AVF), abdominal subcutaneous fat (ASF), and abdominal total fat (ATF) were measured using a computed tomography scan, both before (baseline) and after (post) a 20-week endurance exercise training protocol in the HERITAGE Family Study. Each of the baseline and response (post minus baseline) measures was adjusted for several covariates, including total fat mass, and responses to training were further adjusted for baseline levels. Multipoint variance components linkage analysis using a genomewide scan of 344 markers was conducted separately by race using race-specific allele frequencies. Several promising results (P < 0.0023) were obtained. For baseline AVF, the best evidence was on 2q22.1 and 2q33.2-q36.3 (including the IRS1 locus) in whites, with suggestive findings on 7q22.2-q31.3 (including the LEP locus) in blacks. Although several regions were indicated for baseline ASF, only 4q31.22-q32.2 and 11p15.4-p11.2 replicated the results of another study. For responses to training, promising results were limited to ASF and ATF primarily on 7q36.2 (including NOS3) in blacks, with suggestive regions (P < 0.01) on 1q21.2-q24.1 (S100A, ATP1A2, and ATP1B1), 10q25.2 (ADRA2A), and 11p15.5 (IGF2). In summary, the 4q and 11p regions have now been implicated in two independent studies for ASF; further research is warranted to identify the genes and mutations in these regions that are responsible for fat accumulation in the abdominal depot. Additional work in an independent sample is needed to verify the linkages for baseline AVF as well as the response measures.

Abdomen↗

PubMed2002

The alpha 2-adrenergic receptor gene and body fat content and distribution: the HERITAGE Family Study.

BACKGROUND: Among adrenergic receptor subtypes that regulate lipid mobilization, the alpha2-adrenergic receptor is involved in the inhibition of fatty acid mobilization from adipose tissue. A C-1291G polymorphism is located in the alpha2-adrenergic receptor gene (ADRA2A) but no association with body fat accumulation has been reported yet. MATERIALS AND METHODS: Body mass index (BMI), fat mass (FAT), percentage body fat (%FAT), trunk-to-extremity skinfold ratio (TER), sum of eight skinfolds (SF8), and abdominal subcutaneous (ASF), visceral (AVF), and total (ATF) fat areas assessed by CT scan have been measured in adult sedentary white (n = 503) and black (n = 276) subjects participating in the HERITAGE Family Study. Association between the C-1291G polymorphism and each phenotype was tested separately in men and women of each race using ANCOVA with the effects of age as covariate in addition to the effects of BMI for TER and of FAT for AVF, ASF, and ATF. RESULTS: The allele frequencies of the ADRA2A C-1291G polymorphism differed between races. No association was observed in white subjects, except for a moderate effect of the polymorphism accounting for less than 1% of the variance in AVF and ATF in women. In black subjects, however, the G-1291 allele was found to be associated with an increase of TER in men (3.8% of variance accounted for by the polymorphism), while in black women it was associated with a decrease in TER (2.9%) and in AVF (2.5%). CONCLUSION: These results suggest a role for the ADRA2A gene in determining the propensity to store fat in the abdominal area, independently of total body fatness.

Adult↗

PubMed2001

Effect of type 2 diabetes mellitus on left ventricular geometry and systolic function in hypertensive subjects: Hypertension Genetic Epidemiology Network (HyperGEN) study.

BACKGROUND: Type 2 diabetes is a cardiovascular risk factor. It remains to be elucidated in a large, population-based sample whether diabetes is associated with changes in left ventricular (LV) structure and systolic function independent of obesity and systolic blood pressure (BP). METHODS AND RESULTS: Among 1950 hypertensive participants in the HyperGEN Study without overt coronary heart disease or significant valve disease, 20% (n=386) had diabetes. Diabetics were more likely to be women, black, older, and have higher BMI and waist/hip ratio than were nondiabetics. After adjustment for age and sex, diabetics had higher systolic BP, pulse pressure, and heart rate; lower diastolic BP; and longer duration of hypertension than nondiabetics. LV mass and relative wall thickness were higher in diabetic than nondiabetic subjects independent of covariates. Compared with nondiabetic hypertensives, diabetics had lower stress-corrected midwall shortening, independent of covariates, without difference in LV EF. Insulin levels and insulin resistance were higher in non-insulin-treated diabetics (n=195) than nondiabetic (n=1439) subjects (both P:<0.01). Insulin resistance positively but weakly related to LV mass and relative wall thickness. CONCLUSIONS: In a relatively healthy, population-based sample of hypertensive adults, type 2 diabetes was associated with higher LV mass, more concentric LV geometry, and lower myocardial function, independent of age, sex, body size, and arterial BP. structural and functional abnormalities in addition to, and independent of, atherosclerosis.(13) (14) In the Framingham cohort, diabetes was associated with higher LV mass in women but not men.(15) High blood pressure (BP), obesity, and abnormal lipid profile, which often coexist with diabetes, tend to be associated with preclinical cardiovascular abnormalities(16) and may contribute to the association of diabetes with cardiovascular events. Cardiac features of diabetic and nondiabetic hypertensive subjects remain incompletely described in population-based samples. Therefore, we compared clinical and metabolic characteristics, LV geometry, and systolic function between diabetic and nondiabetic hypertensive participants in the Hypertension Genetic Epidemiology Network (HyperGEN) Study.

Adult↗