Body Composition Remodeling and Incident Mobility Limitations in African Ancestry Men.

BACKGROUND: Mobility limitations are common, with higher prevalence in African Americans compared with whites, and are associated with disability, institutionalization, and death. Aging is associated with losses of lean mass and a shift to central adiposity, which are more pronounced in African Americans. We aimed to examine the association of body composition remodeling with incident mobility limitations in older men of African ancestry. METHODS: Seven-year changes in body composition were measured using peripheral quantitative computed tomography (pQCT) of the calf and whole-body dual x-ray absorptiometry (DXA) in 505 African ancestry men aged ≥60 years and free of self-reported mobility limitations at baseline. Self-reported incident mobility limitations were assessed at 7-year follow-up. Odds of developing mobility limitations associated with baseline and change in body composition were quantified using separate logistic regression models. RESULTS: Seventy-five men (14.9%) developed incident mobility limitations over 6.2 ± 0.6 years. Baseline body composition was not associated with incident mobility limitations. After adjustment for covariates, gaining total and intermuscular fat were associated with incident mobility limitations (odds ratio [OR]: 1.60; 95% confidence interval [CI]: 1.21-2.13; OR: 1.51; 95% CI: 1.18-1.94). Changes in DXA lean mass were not related to mobility limitations; however, maintaining pQCT calf muscle area was protective against mobility limitations (OR: 0.65; 95% CI: 0.48-0.87). CONCLUSIONS: Increases in body fat, and particularly intermuscular fat, and decreases in calf skeletal muscle area were associated with a higher risk of developing mobility limitations. Our findings emphasize the importance of body composition remodeling in the development of mobility limitations among African ancestry men.

Association of ectopic fat with abdominal aorto-illiac and coronary artery calcification in african ancestry men.

BACKGROUND AND AIMS: There is strong evidence that fat accumulating in non-adipose sites, "ectopic fat", is associated with cardiovascular disease (CVD), including vascular calcification. Most previous studies of this association have assessed only a single ectopic fat depot. Therefore, our aim was to assess the association of total, regional, and ectopic fat with abdominal aorto-illiac calcification (AAC) and coronary artery calcification (CAC) in 798 African ancestry men. METHODS: Participants (mean age 62) were from the Tobago Bone Health Study cohort. Adiposity was assessed via clinical examination, dual x-ray absorptiometry, and computed tomography (CT). Ectopic fat depots included: abdominal visceral adipose tissue (VAT), liver attenuation, and calf intermuscular adipose tissue (IMAT). Vascular calcification was assessed by CT and quantified as present versus absent. Associations were tested using multiple logistic regression adjusted for traditional cardiovascular risk factors. Models of ectopic fat were additionally adjusted for total body fat and standing height. RESULTS: All adiposity measures, except VAT, were associated with AAC. Lower liver attenuation or greater calf IMAT was associated with 1.2-1.3-fold increased odds of AAC (p < 0.03 for both), though calf IMAT was a stronger predictor than liver attenuation (p < 0.001) when entered in a single model. No ectopic fat measure was associated with CAC. CONCLUSIONS: Greater adiposity in the skeletal muscle and liver, but not in the visceral compartment, was associated with increased odds of AAC in African ancestry men. These results highlight the potential importance of both quantity and location of adiposity accumulation throughout the body.

Serum carotenoid and retinol levels in African-Caribbean Tobagonian men with high prostate cancer risk in comparison with African-American men.

Black men are known to have a higher risk for prostate cancer (PC). Carotenoids and retinol, linked to PC, have not been compared in different black populations at risk. We examined serum carotenoid and retinol levels between PC-free African-Caribbean (AC) Tobagonian men with a high PC risk (high-grade prostatic intraepithelial neoplasia, atypical foci or repeated abnormal PC screenings) and African-American (AA) men with elevated serum prostate-specific antigen (PSA) levels (≥4 ng/ml). AC men who participated in the 2003 lycopene clinical trial and AA men who participated in the 2001-2006 National Health and Nutrition Examination Survey were compared. Serum specimens were analysed for carotenoid (ß-carotene, α-carotene, ß-cryptoxanthin, lutein/zeaxanthin and lycopene) and retinol levels by isocratic HPLC. Quantile regression was used to examine the association between serum carotenoid and retinol levels and black ethnicity, overall and among men with elevated serum PSA. There were sixty-nine AC men and sixty-five AA men, aged 41-79 years, included. AC men were associated with lower serum lycopene and retinol levels, and higher serum α- and ß-carotenes and lutein/zeaxanthin levels compared with AA men, after adjusting for age, BMI, ever smoked cigarettes, education and hypertension (P≤0·03). Among men with elevated PSA, serum retinol was no longer statistically significant with ethnicity (P=0·06). Possible differences may be attributed to dietary intake, genetics and/or factors that influence bioavailability of these micronutrients. Prospective studies are warranted that investigate whether these differences in micronutrients between AC Tobagonian and AA men influence PC risk.

Elevated Serum PSA is Associated With Human Herpesvirus 8 Infection and Increased Circulating Cytokine Levels in Men From Tobago.

BACKGROUND: Serum-prostate specific antigen (PSA) levels have been used for many years as a biomarker for prostate cancer. This usage is under scrutiny due to the fact that elevated PSA levels can be caused by other conditions such as benign prostatic hyperplasia and infections of or injury to the prostate. As a result, the identification of specific pathogens capable of increasing serum levels of PSA is important. A potential candidate responsible for elevated PSA is human herpesvirus 8 (HHV-8). We have reported previously that HHV-8 is capable of infecting and establishing a latent infection in the prostate. In this current study we test the hypothesis that HHV-8 infection is associated with elevated PSA levels. Circulating cytokine levels between men with elevated PSA and controls are also compared. METHODS: HHV-8 serostatus was determined among men with elevated serum PSA (≥4 ng/ml; n = 168, no prostate cancer on biopsy) and age-matched controls (PSA <4 ng/ml; n = 234), Circulating cytokine levels were determined among a subset of each group (116 with elevated PSA and 85 controls). RESULTS: Men with an elevated serum PSA were significantly more likely to be HHV-8 seropositive (42.9%) than the age-matched cancer-free men (22.2%; OR 2.51; 95%CI 1.48-4.29, P = 00001). Comparison of circulating cytokine levels between men with elevated serum PSA and controls indicated that elevated serum PSA is associated with a pro-inflammatory response with a mixed Th1/Th2 response while HHV-8 infection was associated with significantly higher levels of IL12p70, IL-10, and IL-13 indicating a Th2 immune response. CONCLUSIONS: We found a significant association between HHV-8 infection and increased levels of serum PSA. In an age of patient-centered medicine, men with an elevated serum PSA should be considered for HHV-8 serology testing to determine if HHV-8 is responsible for the elevated PSA. Prostate 77: 617-624, 2017. © 2017 Wiley Periodicals, Inc.

Human herpesvirus 8 infection contributes to a T helper 2 immune response in men from Tobago with prostate cancer.

OBJECTIVES: To compare the cytokine profile between human herpesvirus 8 seropositive and seronegative men with and without prostate cancer. METHODS: The study sample was obtained from the Tobago Prostate Survey, an ongoing study of prostate cancer in the Caribbean island of Tobago. Participants in the study were recruited mostly by public service announcement and by word of mouth. For analyses of circulating levels of pro-inflammatory cytokines, participants with biopsy-confirmed prostate cancer (n = 79) were compared with control participants (n = 87). RESULTS: Cytokine analyses showed a T helper 2 response with suppressed T helper 1 response in prostate cancer patients, as evidenced by significantly increased levels of interleukin-13 and reduced levels of interleukin-12p70. Herpesvirus 8 seropositive men showed significantly increased levels of interleukin-13 and interleukin-10. At logistic regression analyses, interleukin-12p70 predicted prostate cancer in 94.4% of human herpesvirus 8 seropositive men. CONCLUSIONS: These findings show that prostate cancer elicits an antitumor, T helper 2 response with a suppressed T helper 1 response. Human herpesvirus 8 infection results in a similar immune response supporting the hypothesis that in Tobago, human herpesvirus 8 establishes a chronic infection that can contribute to an immune response favoring the formation and survival of prostate cancer.

Greater skeletal muscle fat infiltration is associated with higher all-cause mortality among men of African ancestry.

BACKGROUND: fat infiltration within and around skeletal muscle (i.e. myosteatosis) increases with ageing, is greater in African versus European ancestry men and is associated with poor health. Myosteatosis studies of mortality are lacking, particularly among African ancestry populations. METHODS: in the Tobago Health study, a prospective longitudinal study, we evaluated the association of all-cause mortality with quantitative computed tomography (QCT) measured lower leg myosteatosis (intermuscular fat (IM fat) and muscle density) in 1,652 African ancestry men using Cox proportional hazards models. Date of death was abstracted from death certificates and/or proxy. RESULTS: one hundred and twelve deaths occurred during follow-up (mean 5.9 years). In all men (age range 40-91 years), higher all-cause mortality was associated with greater IM fat (HR (95% CI) per SD: 1.29 (1.06-1.57)) and lower muscle density (HR (95% CI) per SD lower: 1.37 (1.08-1.75)) in fully adjusted models. Similar mortality hazard rates were seen in the subset of elderly men (aged ≥65 years) with greater IM fat (1.40 (1.11-1.78) or lower muscle density (1.66 (1.24-2.21)) in fully adjusted models. CONCLUSIONS: our study identified a novel, independent association between myosteatosis and all-cause mortality in African ancestry men. Further studies are needed to establish whether this association is independent of other ectopic fat depots and to identify possible biological mechanisms underlying this relationship.

Human herpesvirus 8 establishes a latent infection in prostates of Tobago men resulting in increased macrophage infiltration.

BACKGROUND: The Caribbean island of Tobago, which is 97% African ancestry, has one of the highest rates of prostate cancer in the world. We have previously reported that human herpesvirus 8 (HHV-8) infection is significantly associated with prostate cancer in Tobago. In this study, we extend those results testing the hypothesis that HHV-8 seropositive Tobagonian men have a chronic HHV-8 infection in their prostates that is associated with increased inflammation. METHODS: Prostate sections were screened by immunohistochemistry for the expression of HHV-8 proteins K8.1 and LANA-1 and for presence of B cells (CD20) and macrophages (CD68). RESULTS: HHV-8 antigen expression representing lytic and latent infections was seen in 73.9% of prostates from HHV-8 seropositive subjects. Latent infections were seen predominantly in glandular epithelia whereas lytic gene expression was seen mainly in macrophages in prostate stroma. Macrophage infiltrates were significantly increased in sections expressing HHV-8 proteins. CONCLUSION: HHV-8 establishes a chronic latent infection in the prostate, which is associated with an increased macrophage infiltrate.

Human herpesvirus 8 seroconversion in a population-based cohort of men in Tobago.

Human herpesvirus 8 (HHV-8) is the causal agent of Kaposi's sarcoma (KS). In Tobago, KS is not common; however, HHV-8 seropositivity has been reported to be 39.9% in men with prostate cancer compared to <22.9% in healthier women and men. To understand HHV-8 transmission, we examined HHV-8 seroconversion and seroreversion, and risk factors for these changes in Tobago men. Serum specimens from a sub-cohort of Tobago Prostate Survey men, aged 40-81 years (n = 381/442), were collected at baseline and a subsequent visit between 3 and 9 years and tested for HHV-8 seropositivity using an immunofluorescence assay for antibodies against HHV-8 lytic antigens. Poisson distribution was used to calculate HHV-8 seroconversion and seroreversion rates and their 95% confidence intervals. Differences in baseline characteristics between HHV-seroconverters versus persistent HHV-8 seronegative men and HHV-8 seroreverters versus HHV-8 seropositive men were examined. HHV-8 seropositivity was 12.3% (N = 381) at baseline, with HHV-8 seropositivity significantly higher in increasing age groups, 40-49 (4.0%) to 70-81 (37.5%) years (P-value trend <0.0001). HHV-8 seroconversion and seroreversion rates were 0.23 per 100 person-years (95% C.I., 0.06-0.58) and 2.42 per 100 person-years (95% C.I., 0.89-5.26), respectively. There were significantly more HHV-8 seroconverters who reported "ever smoked cigarettes of >6 months" at baseline compared to HHV-8 persistent seronegative men (P-value = 0.03). Baseline characteristics of HHV-8 seroreverters did not differ from persistent seropositive men. Low HHV-8 seroconversion and seroreversion rates were found. Data suggest that HHV-8 transmission occurred at earlier ages, <40 years, in Tobago men.

Association of circulating sclerostin with vascular calcification in Afro-Caribbean men.

OBJECTIVE: Sclerostin, a Wingless (Wnt) pathway antagonist, is an established regulator of bone mineralization in humans but its potential importance in the regulation of vascular calcification is less clear. Therefore, our objective was to assess the relationship of serum sclerostin levels with coronary and aortic artery calcification (CAC and AAC, respectively) in Afro-Caribbean men on the island of Tobago. METHODS: Serum sclerostin levels and computed tomography of CAC and AAC were measured in 191 men (age mean(SD): 62.9(8.0)years) recruited without regard to health status. Multivariable logistic regression models were used to assess the cross-sectional association of sclerostin with prevalent arterial calcification. RESULTS: Mean(SD) sclerostin was 45.2 pmol/L (15.6 pmol/L). After adjusting for risk factors including age, physical and lifestyle characteristics, comorbidities, lipoproteins and kidney function, 1 SD greater sclerostin level was associated with a 1.61-times (95%CI 1.02-2.53) greater odds of having CAC. Sclerostin was not associated with AAC in any model. CONCLUSIONS: This is the first study to show that, among Afro-Caribbean men, greater serum sclerostin concentrations were associated with prevalence and extent of CAC. Further studies are needed to better define the role of the Wnt signaling pathway in arterial calcification in humans.

Risk factors for fracture in middle-age and older-age men of African descent.

Although fracture rates are lower in individuals of African descent compared to individuals of European ancestry, morbidity and mortality following a fracture may be greater in individuals of African ancestry. However, fracture risk and associated clinical risk factors have not been well-defined among African ancestry populations, especially among men of African ancestry. We used data collected from the Tobago Bone Health Study to examine potential clinical risk factors for incident fractures, including demographic information, anthropometric measurements, medical history, lifestyle factors, bone mineral density (BMD), and hip structural geometry. Among 1933 Afro-Caribbean men aged ≥40 years at study entry (mean age: 57.2 ± 11.0 years), 65 reported at least one new fracture during 10 years of subsequent follow-up. Younger age, mixed Afro-Caribbean ancestry, prior fracture history, BMD, and hip structural geometry were statistically significant risk factors for incident fractures. A 1-SD change in several skeletal parameters (hip BMD, cross-sectional area, outer diameter, cortical thickness, and buckling ratio) were each associated with a 35% to 56% increase in incident fracture risk after adjusting for age. Men with a prior fracture history were three times more likely to experience a new fracture during follow-up, and the association remained strong after adjusting for age, mixed Afro-Caribbean ancestry, and skeletal parameters (hazard ratios ranged from 2.72 to 2.82). Our findings suggest that except for age, risk factors for fracture in men of African ancestry are similar to established risk factors in white populations. Prior fracture history is a powerful and independent risk factor for incident fractures among men of African ancestry and could easily be incorporated into clinical risk evaluation.

Genetic epidemiology and genome-wide linkage analysis of carotid artery ultrasound traits in multigenerational African ancestry families.

OBJECTIVE: Intima-media thickness, adventitial diameter and lumen diameter are indicators of cardiovascular disease risk. The influence of genetic factors on these measures in African ancestry populations is not well defined. Therefore, we estimated heritability and performed genome-wide linkage analysis of carotid ultrasound traits in 7 multigenerational families of African ancestry. METHODS: A total of 395 individuals (7 pedigrees; mean family size = 56; 2392 relative pairs) aged ≥18 years had a common carotid artery ultrasound scan. Statistical analyses were conducted using pedigree-based maximum likelihood methods. RESULTS: Significant covariates included age, sex, body mass index or height and waist, and systolic blood pressure. Residual heritabilities ranged from 0.35 ± 0.10 to 0.64 ± 0.12 (P < 0.0001). We identified a novel quantitative trait locus for adventitial and lumen diameters on chromosome 11 (max LOD = 4.09, 133 cm). CONCLUSION: Further fine mapping of this region may identify specific mutations predisposing to subclinical vascular disease among African ancestry individuals.

Patterns and correlates of grip strength change with age in Afro-Caribbean men.

BACKGROUND: muscle strength is essential for physical functions and an indicator of morbidity and mortality in older adults. Among the factors associated with muscle strength loss with age, ethnicity has been shown to play an important role. OBJECTIVE: to examine the patterns and correlates of muscle strength change with age in a population-based cohort of middle-aged and older Afro-Caribbean men. METHODS: handgrip strength and body composition were measured in 1,710 Afro-Caribbean men. Data were also collected for demographic variables, medical history and lifestyle behaviours. RESULTS: the age range of the study population was 29-89 years. Grip strength increased below age 50 years, and decreased after age 50 years over 4.5-year follow-up. The average loss in grip strength was 2.2% (0.49% per year) for ages 50 years or older and 3.8% (0.64% per year) for ages 65 years or older. The significant independent predictors of grip strength loss included older age, a greater body mass index, lower initial arm lean mass and greater loss of arm lean mass. CONCLUSION: Afro-Caribbean men experience a significant decline in muscle strength with advanced age. The major independent factors associated with strength loss were similar to other ethnic groups, including age, body weight and lean mass.

Chromosome 8q24 variants are associated with prostate cancer risk in a high risk population of African ancestry.

BACKGROUND: Earlier studies on the role of germline variations in the disproportionate higher burden of prostate cancer in men of African ancestry have been largely unrewarding. However, the successful replication of recent genome-wide association findings implicating some regions of chromosome 8q24 in the disparate prostate cancer susceptibility in men of European and African ancestry have been encouraging. This case-control study was designed to evaluate the association between germline variations in chromosome 8q24 and prostate cancer risk in Afro-Caribbean Tobago men, a population of predominantly West African ancestry. METHODS: High molecular weight genomic DNA was isolated from blood clots using Qiagen kits. Genotyping was performed on genomic DNA using a pre-designed TaqMan SNP assay according to the manufacture's protocol on a 7900HT Fast Real-Time PCR system (Applied Biosystems, Foster City, CA). RESULTS: SNP rs16901979 in region 2 was associated with significantly increased risk of prostate cancer (OR = 1.41, 95% confidence interval [CI] 1.02-1.95, P = 0.04) with the risk stronger in men with early-onset prostate cancer (OR = 2.37, 95% CI 1.40-3.99, P = 0.001). There was a tendency towards significantly increased risk for SNPs rs1447295 and rs6983267 in men with early-onset prostate cancer. CONCLUSIONS: The replication of the association of chromosome 8q24 variants with increased prostate cancer risk in Tobago men and the higher frequency of the risk alleles in controls in populations of African ancestry further strengthens the possible role of this genomic region in the disproportionate higher burden of prostate cancer in men of African ancestry.

Low prevalence of vitamin D deficiency in elderly Afro-Caribbean men.

Vitamin D deficiency is highly prevalent worldwide, and is linked to several major chronic, inflammatory and autoimmune diseases. Vitamin D deficiency has not been evaluated in dark skinned individuals living in areas of high sun exposure utilizing more reliable mass spectrometry assay techniques. We determined the prevalence of 25-hydroxyvitamin D (25(OH)D) deficiency in Afro-Caribbean men on the tropical island of Tobago, where there is a high level of sunshine year round. Serum 25(OH)D2 and 25(OH)D3 metabolites were measured following extraction and purification using liquid chromatography and tandem mass spectrometry in 424 Afro-Caribbean men aged > 65 years from a larger population-based cohort study. The mean (+/- SD) serum total 25(OH)D concentration was 35.1 +/- 8.9 ng/mL. Deficiency (< 20 ng/mL) was present in only 2.8% and insufficiency (< 30 ng/mL) in 24% of the men. Multiple linear regression analysis identified age, BMI and daily vitamin D supplementation as the independent correlates of 25(OH)D. None of the men who consumed fish more than once per week had vitamin D deficiency, compared to 4% of the men who consumed fish once per week or less (P = .01, adjusted for age, BMI, and daily vitamin D supplementation). In conclusion, vitamin D deficiency is very uncommon in this Afro-Caribbean population. Longitudinal studies are needed to delineate the possible effects of high vitamin D levels in this population on major diseases hypothesized to be associated with vitamin D deficiency.

Markers of inflammation are heritable and associated with subcutaneous and ectopic skeletal muscle adiposity in African ancestry families.

UNLABELLED: Abstract Background: Skeletal muscle adipose tissue (AT) infiltration, or myosteatosis, appears to be greater in African compared with European ancestry individuals and may play a role in type 2 diabetes mellitus (T2DM), a disease that disproportionally affects African ancestry populations. Inflammation is one mechanism that may link myosteatosis with increased T2DM risk, but studies examining the relationship between inflammation and myosteatosis are lacking. METHODS: To examine these associations, we measured skeletal muscle subcutaneous AT, intermuscular AT, and skeletal muscle density using quantitative computed tomography and serum markers of inflammation in 471 individuals from 8 Afro-Caribbean multigenerational families [mean family size 67; mean age 43 years; mean body mass index (BMI) 28 kg/m(2)]. RESULTS: After removing the variation attributable to significant covariates, heritabilities of inflammation markers [C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α)] ranged from 33% (TNFα) to 40% (CRP); all P<0.01. Higher CRP, IL-6, and TNF-α were associated with lower subcutaneous AT around skeletal muscle (r=-0.13 to -0.19, P<0.05). Higher CRP was additionally associated with lower skeletal muscle density, indicative of greater intramuscular AT (r=-0.10, P<0.05), hyperinsulinemia (r=0.12, P<0.05), and increased homeostasis model assessment of insulin resistance (HOMA-IR) (r=0.17, P<0.01). CONCLUSIONS: Our findings suggest that heredity may play a significant role in the determination of several markers of inflammation in African ancestry individuals. Higher concentrations of CRP appear to be associated with greater skeletal muscle AT infiltration, lower subcutaneous AT, hyperinsulinemia, and insulin resistance. Longitudinal studies are needed to further evaluate the relationship between inflammation with changes in skeletal muscle AT distribution with aging and the incidence of T2DM.

Bioactive androgens and glucuronidated androgen metabolites are associated with subcutaneous and ectopic skeletal muscle adiposity among older black men.

Aging is associated with declining serum levels of androgenic hormones and with increased skeletal muscle fat infiltration, an emerging risk factor for type 2 diabetes mellitus (T2DM). Androgens regulate fat mass and glucose homeostasis, but the effect of androgenic hormones on skeletal muscle fat infiltration is largely unknown. Thus, the aim of the current study was to examine the association of serum androgens and their precursors and metabolites with skeletal muscle fat infiltration and T2DM in a black male population group at high risk of T2DM. Serum androgens, estrogens, and androgen precursors and metabolites were measured using mass spectrometry; and calf skeletal muscle fat distribution (subcutaneous and intermuscular fat; skeletal muscle density) was measured using quantitative computed tomography in 472 Afro-Caribbean men 65 years and older. Bioactive androgens, testosterone, free testosterone, and dihydrotestosterone were associated with less skeletal muscle fat infiltration (r = -0.14 to -0.18, P < .05) and increased skeletal muscle density (r = 0.10 to 0.14, P < .05), independent of total adiposity. In addition, glucuronidated androgen metabolites were associated with less subcutaneous fat (r = -0.11 to -0.15, P < .05). Multivariate logistic regression analysis identified an increased level of 3α-diol-3 glucuronide (odds ratio = 1.38, P < .01) and a decreased level of dihydrotestosterone (odds ratio = 0.66, P < .01) to be significantly associated with T2DM. Our findings suggest that, in elderly black men, independent of total adiposity, bioactive androgens and glucuronidated androgen metabolites may play previously unrecognized role in skeletal muscle fat distribution. Longitudinal studies are needed to further evaluate the relationship between androgens and androgen metabolites with changes in skeletal muscle fat distribution with aging and the incidence of T2DM.

ADRB2 gene variants, dual-energy x-ray absorptiometry body composition, and hypertension in Tobago men of African descent.

Classic tissue effects of ß(2)-adrenergic receptor activation include skeletal muscle glycogenolysis and vascular smooth muscle relaxation, factors relevant to obesity and hypertension, respectively. In a population-based study, we examined 2 common amino acid substitutions in the ß(2)-adrenergic receptor gene (ADRB2) in relation to body composition and blood pressure. A cross-sectional analysis of 1893 African-descent men living in Tobago and participating in a prostate cancer screening study was performed. Body mass index, waist circumference, blood pressure, dual-energy x-ray absorptiometry body composition, and ADRB2 (Arg16Gly; Gln27Glu) genotype were determined. Twenty-six percent were obese (body mass index ≥30 kg/m(2)), and 50% were hypertensive. ADRB2 Arg16Gly and Gln27Glu alleles were in linkage disequilibrium (D' = 0.96, r(2) = 0.15). ADRB2 16Gly-containing and 27Glu-containing genotypes were equally frequent in low, medium, and high tertiles of percentage of body fat mass (16Gly-containing genotypes: 73.4%, 74.4%, and 74.5%, P(trend) = .66; 27Glu-containing genotypes: 27.6%, 23.8%, and 25.4%, P(trend) = .39) and in normal blood pressure, prehypertensive, and hypertensive men (16Gly-containing genotypes: 73.4%, 72.8%, and 74.4%, P(trend) = .61; 27Glu-containing genotypes: 25.6%, 24.1%, and 26.7%, P(trend) = .50). In a high-obesity and high-hypertension risk population with ancestry in common with African Americans, genetic variation defined by 2 common ADRB2 amino acid substitutions was not associated with body composition or hypertension.

Adipose tissue and volumetric bone mineral density of older Afro-Caribbean men.

Although low body weight is a risk factor for osteoporosis-related fractures, conflicting data exist for the association between adiposity and bone mineral density (BMD). Studies examining these relationships have measured body fat and BMD with dual-energy X-ray absorptiometry (DXA), which cannot distinguish subcutaneous adipose tissue area (SAT) from total adiposity or trabecular from cortical bone. To investigate the relationship between adiposity and BMD further, we analyzed body composition and adipose tissue distribution by quantitative computed tomography (QCT) in 1829 Afro-Caribbean men aged 40 years and older from a population-based sample. Cortical volumetric BMD, muscle cross-sectional area, total adipose tissue area (TAT), and percentage SAT were measured at the proximal tibia. Trabecular volumetric BMD was measured at the distal tibia. We used analysis of covariance to test for associations between quartile of the adipose tissue measures and BMD, adjusting for anthropometric, health, and lifestyle factors. Higher TAT was associated with lower cortical BMD in both unadjusted and adjusted models (p < .001). Men with a higher percentage SAT had greater cortical BMD (p < .001). Similar associations were seen between percent SAT and trabecular BMD at the distal tibia. These results indicate that total adiposity is a potentially important correlate of bone mass in older men and that different fat depots may have opposing associations with bone mass. Additional research is needed to better understand the mechanisms underlying the relationship between body fat distribution and bone mass.

Association of the CPT1B gene with skeletal muscle fat infiltration in Afro-Caribbean men.

Skeletal muscle fat is greater in African ancestry individuals compared with whites, is associated with diabetes, and is a heritable polygenic trait. However, specific genetic factors contributing to skeletal muscle fat in humans remain to be defined. Muscle carnitine palmitoyltransferase-1B (CPT1B) is a key enzyme in the regulation of skeletal muscle mitochondrial beta-oxidation of long-chain fatty acids, and as such is a reasonable biological candidate gene for skeletal muscle fat accumulation. Therefore, we examined the association of three nonsynonymous coding variants in CPT1B (G531L, I66V, and S427C; a fourth, A320G, could not be genotyped) and quantitative computed tomography measured tibia skeletal muscle composition and BMI among 1,774 Afro-Caribbean men aged > or =40, participants of the population-based Tobago Health Study. For all variants, no significant differences were observed for BMI or total adipose tissue. Among individuals who were homozygous for the minor allele at G531L or I66V, intermuscular adipose tissue (IMAT) was 87% (P = 0.03) and 54% lower (P = 0.03), respectively. In contrast, subcutaneous adipose tissue (SAT) was 11% (P = 0.017) and 7% (P = 0.049) higher, respectively, than among individuals without these genotypes. These associations were independent of age, body size, and muscle area. Finally, no individuals with type 2 diabetes were found among those who were homozygous for the minor allele of either at G531L and I66V whereas 14-18% of men with the major alleles had type 2 diabetes (P = 0.03 and 0.007, respectively). Our results suggest a novel association between common nonsynonymous coding variants in CPT1B and ectopic skeletal muscle fat among middle-aged and older African ancestry men.

Correlates of trabecular and cortical volumetric BMD in men of African ancestry.

QCT provides a measure of volumetric BMD (vBMD) and distinguishes trabecular from cortical bone. Few studies have determined the factors related to vBMD in men, especially among men of African heritage. This study evaluated the relationship of anthropometric, medical, and behavioral factors and vBMD in a population-based cohort of men of African ancestry (n = 1901) >or=40 yr of age who had undergone screening for prostate cancer for the first time. Trabecular and cortical vBMD were measured at the radius and tibia by pQCT. Multiple linear regression analysis identified age, height, body weight, cigarette smoking, history of diabetes, fracture, and prostate cancer as the independent correlates of vBMD. However, associations with several variables differed between cortical and trabecular vBMD and between the radius and tibia. Longitudinal studies are needed to gain a better understanding of the mechanisms underlying these differential associations that may show new insight into the etiology of trabecular and cortical bone loss in men.