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Objective: Increased fat infiltration in skeletal muscle has been associated with diabetes. Quantitative computed tomography (QCT) can be used to measure muscle density, which reflects the lipid content of skeletal muscle such that greater fat infiltration in skeletal muscle is associated with lower muscle density. The relative contribution of genetic and environmental factors to fat infiltration in skeletal muscle has not been assessed. Therefore, our aim is to determine genetic and environmental contributions to measures of skeletal muscle composition, and describe their associations with type 2 diabetes in multigenerational families of African ancestry. Methods and Procedures: Peripheral QCT (pQCT) measures of skeletal muscle density were obtained for the calf in 471 individuals (60% women; mean 43 years) belonging to eight large, multigenerational Afro-Caribbean families (mean family size 51 individuals; 3,535 relative pairs). Results: The proportion of variance in muscle density due to additive genetic effects (residual heritability) was 35.0% (P < 0.001) and significant covariates (age, gender, BMI, and parity) explained 55.0% of the total phenotypic variation in muscle density. Muscle density was lower (P < 0.001) in 62 diabetics (69.5 mg/cm3) than in 339 nondiabetics (74.3 mg/cm3) and remained significant after adjusting for age, gender, and BMI (P = 0.005) or age, gender, and waist circumference (P = 0.01). Discussion: Our results provide new evidence that ectopic lipid deposition in skeletal muscle is a heritable trait and is associated with diabetes, independent of overall and central obesity in families of African heritage. Genome-wide screens and candidate gene studies are warranted to identify the genetic factors contributing to ectopic deposition of skeletal muscle fat.

Despite a higher prevalence of coronary heart disease risk factors, men of African origin have less coronary atherosclerosis, as measured by coronary calcification, than whites. In part, this is thought to be because of the less atherogenic lipoprotein profile observed in men of African origin, characterized by lower triglycerides and higher high-density lipoprotein (HDL) cholesterol. We hypothesized that the -514C>T polymorphism in the hepatic lipase gene (LIPC) plays a significant role in determining a less atherogenic lipoprotein profile observed in men of African origin. Previously conducted studies of the LIPC -514C>T polymorphism in African Americans may have been confounded by a higher level of European admixture; in addition, the results from these studies do not necessarily apply to other African populations because gene-environment interactions may differ. Thus, we compared nuclear magnetic resonance spectroscopy-measured lipoprotein subclass patterns and LIPC -514C>T genotypes in population-based samples of older white American (n = 532) and African American (n = 97) men from the Cardiovascular Health Study to those among older, less admixed, Afro-Caribbean men (n = 205) from the Tobago Health Study. Men of African origin had a more favorable lipoprotein profile than whites. In addition, levels of low-density lipoprotein cholesterol, total cholesterol, and triglyceride, and large and small very low-density lipoprotein, small low-density lipoprotein, as well as very low-density lipoprotein particle size, were remarkably lower in Afro-Caribbean men than in either African American or white men. The frequency of the LIPC -514T allele was much higher in Afro-Caribbeans (0.57) and in African Americans (0.49) than in whites (0.20). The -514T allele in both populations of African origin, but not in whites, was associated with elevated large HDL and greater HDL size. Our findings indicate that the higher frequency of the LIPC -514T allele found in men of African origin living in different environments significantly contributes to the more favorable distribution of HDL subclasses compared with whites.

Background/Aims: The Tobago Afro-Caribbean population is a valuable resource for studying the genetics of diseases that show significant differences in prevalence between populations of African descent and populations of other ancestries. Empirical confirmation of low European and Native American admixture may help in clarifying the ethnic variation in risk for such diseases. We hypothesize that the degree of European and Native American admixture in the Tobago population is low. Methods: Admixture was estimated in a random sample of 220 men, from a population-based prostate cancer screening survey of 3,082 Tobago males, aged 40 to 79 years. We used a set of six autosomal markers with large allele frequency differences between the major ethnic populations involved in the admixture process, Europeans, Native Americans and West Africans. Results: The ancestral proportions of Tobago population are estimated as 94.0 ± 1.2% African, 4.6 ± 3.4% European and 1.4 ± 3.6% Native American. Conclusions: We conclude that Tobago Afro-Caribbean men are predominantly of West African ancestry, with minimal European and Native American admixture. The Tobago population, thus, may carry a higher burdenof high-risk alleles of African origin for certain diseases than the more admixedAfrican-American population. Conversely, this population may benefit from a higher prevalence of protective alleles of African origin.

Both indices of obesity and lipoprotein subfractions contribute to coronary heart disease risk. However, associations between indices of obesity and lipoprotein subfractions remain undetermined across different ethnic groups. This study aims to examine the associations of indices of obesity in Japanese Americans (JA), African Americans (AA) and Koreans with lipoprotein subfractions.A population-based sample of 230 JA, 91 AA, and 291 Korean men aged 40-49 was examined for indices of obesity, i.e., visceral and subcutaneous adipose tissue (VAT and SAT, respectively), waist circumference (WC), and body-mass index (BMI), and for lipoprotein subfractions by nuclear-magnetic-resonance spectroscopy. Multiple regression analyses were performed in each of the three ethnic groups to examine the associations of each index of obesity with lipoprotein.VAT had significant positive associations with total and small low-density lipoprotein (LDL) and a significant negative association with large high-density lipoprotein (HDL) in all three ethnicities (p0.01). SAT, WC, and BMI had significant positive associations with total and small LDL in only JA and Koreans, while these indices had significant inverse associations with large HDL in all ethnic groups (p0.01). Compared to SAT, VAT had largerVAT is significantly associated with total and small LDL and large HDL in all three ethnic groups. The associations of SAT, WC, and BMI with lipoprotein subfractions are weaker compared to VAT in all three ethnic groups.

The relation between cholesteryl ester transfer protein (CETP) levels and atherosclerosis is controversial. We examined whether the serum CETP levels were associated with subclinical atherosclerosis, independent of its most common gene variant, in a sample of Japanese men. A population-based cross-sectional study of 250 Japanese men aged 40 to 49 years was conducted to assess the intima-media thickness of the carotid artery, coronary artery calcium, serum CETP levels, and the CETP D442G gene variant. Compared with the lowest CETP quartile, the multivariate adjusted odds ratio for coronary artery calcium was 0.77 (95% confidence interval 0.18 to 3.36), 0.96 (95% confidence interval 0.27 to 3.40), and 3.49 (95% confidence interval 1.05 to 11.6) with increasing CETP quartiles. The serum CETP quartiles were also positively associated with the intima-media thickness of the carotid artery (adjusted mean 602, 616, 615, and 646 mum for the lowest to top quartile, respectively). The findings remained unchanged after additional adjustment for the CETP D442G gene variant. No significant difference was found in the prevalence of coronary artery calcium or in the mean intima-media thickness of the carotid artery between participants with and without the CETP D442G gene variant.

Background: Although obesity is strongly associated with diabetes, the greater prevalence of diabetes in persons of African ancestry than in those of other ancestries cannot be explained simply by differences in total or central adiposity. Objective: We examined whether skeletal muscle composition is associated with diabetes in 1249 men of African ancestry aged ≥40 y. Design: Anthropometry and fasting serum glucose were measured, and lower-leg skeletal muscle composition was assessed with peripheral quantitative computerized tomography (pQCT). Results: The prevalence of diabetes in this population was high (21%). We observed an age-associated adipose tissue remodeling in skeletal muscle and greater intermuscular (IMAT) and lesser subcutaneous (SAT) adipose tissue area with advancing age (P < 0.0001). Multivariate stepwise logistic regression identified more IMAT and less SAT to be significantly associated with a greater prevalence of diabetes. Even among normal-weight men [body mass index (BMI; in kg/m 2 ) < 25], diabetic men had significantly (P = 0.01) more IMAT than did those without diabetes. Greater IMAT was also associated with a greater prevalence of hyperglycemia in men with a family history of diabetes than in those without such history (P for interaction = 0.02). Conclusions: These findings underscore the independent associations of subcutaneous and intermuscular fat among men of African ancestry, an effect that may be modified by a family history of diabetes. Further studies are needed to identify the genetic and physiologic mechanisms that influence the distribution and remodeling of adipose tissue in skeletal muscle with aging.

Very few studies have comprehensively defined the genetic and environmental influences on body fat storage in the arms and legs and their association with diabetes, especially in families of African heritage. We analyzed body fat distribution by dual-energy x-ray absorptiometry (percentage total fat, percentage trunk fat, percentage arm fat, and percentage leg fat) and fasting serum glucose in 471 individuals (mean age, 43 years) from 8 multigenerational Afro-Caribbean families (mean family size = 51; 3535 relative pairs). Diabetes was inversely associated with percentage leg fat (P = .009) and, to some extent, positively associated with percentage arm fat independent of age, sex, and body size (P = .08), but not with anthropometric or dual-energy x-ray absorptiometric measures of total and central adiposity. Furthermore, percentage leg fat was inversely, whereas percentage arm fat was positively, associated with body mass index, waist circumference, and serum glucose (P.01). Residual heritability (h2r) for arm and leg fat was significant (P.01) and high: 62% (for percentage arm fat) and 40% (for percentage leg fat). Moreover, sex-specific h2r for leg fat was considerably higher (P = .02) in women than in men (h2r values, 58% vs 17%, respectively). Genetic correlation (rho(G)) between arm and leg fat was -0.61 (P.01), suggesting that only 37% of the covariation between these 2 adipose tissue depots may be due to shared genetic influences. This study provides new evidence for a strong genetic and sex contribution to upper and lower body fat, with relatively little covariation between these traits due to shared genes. Our findings also suggest that, in this population, leg fat is associated with diabetes independent of overall adiposity.

The aim of this study was to estimate the heritability of and environmental contributions to skeletal muscle phenotypes (appendicular lean mass and calf muscle cross-sectional area) in subjects of African descent and to determine whether heritability estimates are impacted by sex or age. Body composition was measured by dual-energy X-ray absorptiometry and computed tomography in 444 men and women aged 18 yr and older (mean: 43 yr) from eight large, multigenerational Afro-Caribbean families (family size range: 21–112). Using quantitative genetic methods, we estimated heritability and the association of anthropometric, lifestyle, and medical variables with skeletal muscle phenotypes. In the overall group, we estimated the heritability of lean mass and calf muscle cross-sectional area (h2 = 0.18–0.23, P < 0.01) and contribution of environmental factors to these phenotypes ( r2 = 0.27–0.55, P < 0.05). In our age-specific analysis, the heritability of leg lean mass was lower in older vs. younger individuals (h2 = 0.05 vs. 0.23, respectively, P = 0.1). Sex was a significant covariate in our models ( P < 0.001), although sex-specific differences in heritability varied depending on the lean mass phenotype analyzed. High genetic correlations (ρG = 0.69–0.81; P < 0.01) between different lean mass measures suggest these traits share a large proportion of genetic components. Our results demonstrate the heritability of skeletal muscle traits in individuals of African heritage and that heritability may differ as a function of sex and age. As the loss of skeletal muscle mass is related to metabolic abnormalities, disability, and mortality in older individuals, further research is warranted to identify specific genetic loci that contribute to these traits in general and in a sex- and age-specific manner.

Adipocytokines are a subset of cytokines produced by adipose tissue and are associated with risk of type II diabetes and atherosclerosis. Levels of adipocytokines differ between Black and White Americans, even after adjustment for differences in adiposity, diseases associated with adipocytokines including type 2 diabetes and cardiovascular disease, and general socioeconomic status indicators such as income. We used a series of ancestry informative markers to estimate genetic ancestry in a population-based study of older Black Americans, and examined the association between genetic ancestry and adipocytokines and soluble receptors to help determine which of these may be most amenable to admixture mapping. We typed 35 ancestry informative markers in 1,241 self-reported Black Americans with available DNA from the Health, Aging, and Body Composition (Health ABC) study with available DNA and used a maximum likelihood approach to estimate percent European ancestry. We used linear regression models to determine the association between these adipocytokines and percent ancestry, and staged models to examine whether adiposity or other measures affected the associations of genetic ancestry and adipocytokines. Mean European ancestry was 22.3+/-15.9%. In multivariate adjusted models, the strongest associations observed were between higher European ancestry and interleukin-6 soluble receptor (IL-6 SR), C-reactive protein (CRP), and adiponectin levels, with interleukin-2 soluble receptor (IL-2 SR) and soluble tumor necrosis factor receptor II (TNF-alpha SR II) also showing more modest but significant associations. The association with adiponectin became stronger after adjustment for adiposity. These novel findings suggest that admixture mapping may identify genetic factors influencing the levels of IL-6 SR, CRP, IL-2 SR, and adiponectin.

Adiponectin, an adipose-specific protein, is negatively associated with adiposity, insulin sensitivity, and diabetes. Very few studies have examined the role of heredity in the regulation of adiponectin and its association with body fat among individuals of African heritage. Thus, we measured fasting serum adiponectin levels by radioimmunoassay and body composition by dual-energy x-ray absorptiometry (DEXA) in 402 individuals aged 18 to 103 years belonging to 7 multigenerational families of African heritage in the relatively homogeneous island population of Tobago. Heritability of adiponectin was 33.2% (P < .01), and age, sex, and body mass index explained 23.4% of the variance in adiponectin. Sex-specific heritability was significant in men (heritability, 34%; P < .05), but not in women. The inverse associations between body mass index and percentage of body fat and adiponectin, independent of age and height, were much stronger in women (all P values

Objectives To estimate the prostate cancer screening parameters in a population-based study of African-Caribbean men from the Island of Tobago. Methods A total of 2582 men aged 40 to 79 years (50% of all Tobago men in this age group) were screened using both serum prostate-specific antigen (PSA) and digital rectal examination (DRE). Men with an elevated PSA level (4 ng/mL or greater) or abnormal DRE findings were referred for ultrasound-guided sextant biopsy. Results The screening results for one or both tests were abnormal in 32% of men. The prevalence of prostate cancer was 10.7 of 100 screened men. The positive predictive value for PSA was 56% compared with 39% for DRE. The positive predictive value for PSA ranged from 6% for those aged 40 to 49 years to 59% for those aged 70 to 79 years. The sensitivity was 71% and the specificity 86% for DRE. The sensitivity for PSA was 80%. The sensitivity was low among men aged 40 to 49 years (20%) and 50 to 59 years (66%). The specificity for PSA declined across age groups from 98% for those aged 40 to 49 years to 70% for those 70 to 79 years. Conclusions The screening parameters in this African-Caribbean population were similar to the sparse data available from other populations of African descent. The screening was highly efficacious, with a positive predictive value of 56% for an elevated PSA level and 40% for an elevated PSA level and/or abnormal DRE findings.

Background: Both indices of obesity and lipoprotein subfractions contribute to coronary heart disease risk. However, associations between indices of obesity and lipoprotein subfractions remain undetermined across different ethnic groups.Objective: This study aims to examine the associations of indices of obesity in Japanese Americans, African Americans, and Koreans with lipoprotein subfractions.Methods: A population-based sample of 230 Japanese American, 91 African American, and 291 Korean men ages 40 to 49 was examined for indices of obesity—that is, visceral and subcutaneous adipose tissue (VAT and SAT, respectively); waist circumference; and body mass index—and for lipoprotein subfractions by nuclear magnetic resonance spectroscopy. Multiple regression analyses were performed in each of the 3 ethnic groups to examine the associations of each index of obesity with lipoprotein.Conclusions: VAT had significant positive associations with total and small low-density lipoprotein (LDL) and a significant negative association with large high-density lipoprotein (HDL) in all 3 ethnicities (p < 0.01). SAT, waist circumference, and body mass index had significant positive associations with total and small LDL in only Japanese Americans and Koreans, whereas these indices had significant inverse associations with large HDL in all ethnic groups (p < 0.01). Compared with SAT, VAT had larger R2 values in the associations with total and small LDL and large HDL in all 3 ethnic groups. VAT is significantly associated with total and small LDL and large HDL in all 3 ethnic groups. The associations of SAT, waist circumference, and body mass index with lipoprotein subfractions are weaker than the associations of VAT in all 3 ethnic groups.