Optimal serum cholesterol concentrations are associated with accelerated bone loss in African ancestry men.

UNLABELLED: We tested if serum lipid and lipoprotein cholesterol levels are associated with longitudinal measures of bone mineral density (BMD) in 1289 African ancestry men. After 6 years of mean follow-up, men with clinically optimal levels of low-density lipoprotein (LDL), high-density lipoprotein (HDL), or triglycerides at baseline experienced the greatest BMD loss, independent of potential confounding factors (all p < 0.05). INTRODUCTION: Studies of lipid and lipoprotein cholesterol associations with bone mineral density (BMD) and bone loss have been inconclusive, and longitudinal data are sparse. Therefore, the aim of this study was to test if fasting serum lipid and lipoprotein cholesterol levels are associated with areal and volumetric BMD and BMD change. METHODS: We determined the association of serum triglycerides, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) cholesterol concentrations with cross-sectional and longitudinal (mean follow-up, 6.1 years) measures of BMD in a cohort of 1289 in African ancestry men (mean age, 56.4 years). Fasting serum triglycerides, HDL, and LDL were measured at baseline concurrent with BMD assessments. Dual-energy X-ray absorptiometry was used to quantify integral hip BMD, and peripheral quantitative computed tomography at the radius and tibia was used to quantify volumetric BMD. Men were categorized as optimal, borderline, or high risk for triglyceride, HDL, and LDL concentrations based on Adult Treatment Panel III guidelines. RESULTS: Lower serum triglyceride or LDL and higher HDL concentrations were associated with lower trabecular BMD at baseline (all p < 0.05). Similarly, men classified as having optimal levels of LDL, HDL, or triglycerides at baseline experienced the greatest integral BMD loss at the hip and trabecular BMD loss at the tibia (all p < 0.05), independent of potential confounding factors. CONCLUSIONS: We found that clinically optimal serum lipid and lipoprotein cholesterol concentrations were associated with accelerated bone loss among Afro-Caribbean men. Further studies are needed to better understand the mechanisms involved and potential clinical significance of these findings.

Prevalence and incidence of clinically recognized cases of Type 1 diabetes in children and adolescents in Rwanda, Africa.

AIMS: To determine prevalence and incidence estimates for clinically recognized cases of Type 1 diabetes from the Life For a Child Program (LFAC) with onset < 26 years in six representative districts, and the capital, of Rwanda. METHODS: Cases were identified from the LFAC registry and visits to district hospitals. Denominators were calculated from district-level population surveys. Period prevalence data were collected from 1 August 2011 to 31 July 2012 and annual incidence rates were calculated, retrospectively, for 2004-2011. Ninety-five per cent confidence intervals (95% CI) were calculated using a Poisson distribution. RESULTS: The prevalence of known Type 1 diabetes in seven districts in Rwanda for ages < 26 years was 16.4 [95% CI 14.6-18.4]/100 000 and for < 15 years was 4.8 [3.5-6.4]/100 000. Prevalence was higher in females (18.5 [15.8-21.4]/100 000) than males (14.1 [11.8-16.7]/100 000; P = 0.01) and rates increased with age. The annual incidence rate for those < 26 years was stable between 2007 and 2011 with a mean incidence over that time of 2.7 [2.0-3.7]/100 000 ( < 15 years = 1.2 [0.5-2.0]/100 000). Incidence rates were higher in females than males and peaked in males at ages 17 and 22 years and in females at age 18 years. CONCLUSIONS: Our report of known Type 1 diabetes cases shows lower incidence and prevalence rates in Rwanda than previously reported in the USA and most African countries. Incidence of recognized cases has increased over time, but has recently stabilized. However, the likelihood of missed cases due to death before diagnosis and misdiagnosis is high and therefore more definitive studies are needed.

Association of volumetric bone mineral density with abdominal aortic calcification in African ancestry men.

SUMMARY: We tested for association between cortical and trabecular volumetric bone mineral density (vBMD) with abdominal aortic calcification (AAC) prevalence in 278 Afro-Caribbean men. AAC was present in 68.3 % of the men. Greater cortical, but not trabecular, vBMD was associated with significantly decreased odds of AAC independent of traditional risk factors. INTRODUCTION: The aim of this study is to assess the prevalence and correlates of AAC in a sample of 278 Afro-Caribbean men (mean age 56) and to test for a largely unexplored association between cortical and trabecular vBMD with AAC prevalence. METHODS: Men were recruited consecutively as part of an ongoing prospective cohort study of body composition in men aged 40+. For this analysis, AAC was assessed by computed tomography of the abdomen from L3 to S1. Aortic calcium was scored using the Agatston method, and prevalence was defined as a score ≥10 to rule out false positives. Men also had BMD assessed using peripheral quantitative computed tomography at 4 % (trabecular vBMD) and 33 % (cortical vBMD) of the radius and tibia. RESULTS: Abdominal aortic calcification was present in 68.3 % of the men. Significant independent predictors of AAC prevalence were increased age, increased BMI, hypertension, and current smoking. Age was the strongest predictor, with each SD (7.8 year) increase in age conferring 2.7 times increased odds of having AAC (P < 0.0001). A one SD greater cortical, but not trabecular, vBMD was associated with a significant decreased odds of AAC prevalence independent of other traditional risk factors (OR 0.65; 95 % CI 0.45-0.92). CONCLUSIONS: Cortical vBMD is inversely associated with AAC presence. This finding suggests that there may be shared physiology between cortical bone compartment remodeling and vascular calcification.

Relative influence of heritability, environment and genetics on serum sclerostin.

SUMMARY: We determined factors associated with serum sclerostin in 446 Afro-Caribbean family members. Age, weight, sex, diabetes and kidney function were associated with sclerostin. Sclerostin was heritable, and nine SNPs in the SOST gene region were associated with sclerostin. Variation in serum sclerostin is a heritable factor that is determined by both genetic and environmental factors. INTRODUCTION: Sclerostin, encoded by the SOST gene, is a Wnt inhibitor that regulates bone mineralization and is a candidate gene locus for osteoporosis. However, little is known about the genetic and non-genetic sources of inter-individual variation in serum sclerostin levels. METHODS: Serum sclerostin was measured in 446 Afro-Caribbean men and women aged 18+ from seven large, multigenerational families (mean family size, 64; 3,840 relative pairs). Thirty-six common single nucleotide polymorphisms (SNP) were genotyped within a 100 kb region encompassing the gene encoding sclerostin (SOST). Genetic and non-genetic factors were tested for association with serum sclerostin. RESULTS: Mean serum sclerostin was 41.3 pmol/l and was greater in men than in women (P < 0.05). Factors associated with higher serum sclerostin were increased age and body weight, male sex, diabetes and decreased glomerular filtration rate, which collectively accounted for 25.4 % of its variation. Residual genetic heritability of serum sclerostin was 0.393 (P < 0.0001). Nine SNPs reached nominal significance with sclerostin. Three of those nine SNPs represented independent association signals (rs851056, rs41455049 and rs9909172), which accounted for 7.8 % of the phenotypic variation in sclerostin, although none of these SNPs surpassed a Bonferroni correction for multiple comparisons. CONCLUSIONS: Serum sclerostin is a heritable trait that is also determined by environmental factors including age, sex, adiposity, diabetes and kidney function. Three independent common SNPs within the SOST region may collectively account for a significant proportion of the variation in serum sclerostin.

Genetic analysis of serum osteocalcin and bone mineral in multigenerational Afro-Caribbean families.

UNLABELLED: Osteocalcin is a major component of bone matrix. Concentrations of total, carboxylated, and uncarboxylated osteocalcin, are highly heritable and genetically correlated with bone mineral content (BMC) within African ancestry families. INTRODUCTION: Osteocalcin (OC) is a protein constituent of bone matrix and a marker of bone formation. We characterized the heritability of serum OC measures and identified genomic regions potentially involved in the regulation of OC via high-density genome-wide linkage analysis in African ancestry individuals. METHODS: African ancestry individuals (n = 459) were recruited, without regard to health status, from seven probands (mean family size = 66; 4,373 relative pairs). Residual heritability of serum OC measures was estimated and multipoint quantitative trait linkage analysis was performed using pedigree-based maximum likelihood methods. RESULTS: Residual heritabilities of total OC, uncarboxylated OC, carboxylated OC and percent uncarboxylated OC were 0.74 ± 0.10, 0.89 ± 0.08, 0.46 ± 0.10 and 0.41 ± 0.09, respectively. All OC measures were genetically correlated with whole body BMC. We obtained strong evidence of bivariate linkage for percent uncarboxylated OC and whole body BMC on chromosome 17 (logarithm of the odds [LOD] = 3.15, 99 cM). CONCLUSIONS: All forms of OC were highly heritable and genetically correlated with total body BMC in these African ancestry families. The identified linkage region contains several candidate genes for bone and energy metabolism including COL1A1 and TNFRSF11A. Further studies of this genomic region may reveal novel insight into the genetic regulation of OC and bone mineralization.

Age-related decline in bone density among ethnically diverse older men.

UNLABELLED: We compared rates of BMD decline in older men of diverse ethnic background. The rate of bone loss was statistically equivalent between men of African and Caucasian descent. INTRODUCTION: Race differences in peak bone mineral density (BMD) are well established, but the magnitude of bone loss among non-white men has not been well characterized. Our objective was to compare and contrast the rates of decline in BMD with aging among older men of different race/ethnic groups. METHODS: The rate of decline in hip BMD was measured by dual-energy X-ray absorptiometry (Hologic QDR-4500 W) with an average follow-up of 4.6 years in 3,869 Caucasian, 138 African American, 145 Asian, and 334 Afro-Caribbean men aged ≥ 65 years (Mean ages: 73 ± 5, 70 ± 4, 72 ± 5, 71 ± 5 years, respectively). RESULTS: The annual rate of decline in BMD at the femoral neck was -0.32%, -0.42%, -0.09%, and -0.44%/year for Caucasian, African American, Asian, and Afro-Caribbean men, respectively (p < 0.05 for Caucasian versus Asian). Although men of African ancestry have higher peak BMD than Caucasians, rates of decline in BMD with aging appear to be statistically equivalent in our study. In contrast, Asian men experienced a slower rate of decline in BMD compared with Caucasians and African Americans. CONCLUSION: More studies are needed to better define the natural history of and factors associated with bone loss among non-white men.

Association analysis of 33 lipoprotein candidate genes in multi-generational families of African ancestry.

African ancestry individuals have a more favorable lipoprotein profile than Caucasians, although the mechanisms for these differences remain unclear. We measured fasting serum lipoproteins and genotyped 768 tagging or potentially functional single nucleotide polymorphisms (SNPs) across 33 candidate gene regions in 401 Afro-Caribbeans older than 18 years belonging to 7 multi-generational pedigrees (mean family size 51, range 21-113, 3,426 relative pairs). All lipoproteins were significantly heritable (P<0.05). Gender-specific analysis showed that heritability for triglycerides was much higher (P<0.01) in women than in men (women, 0.62+/-0.18, P<0.01; men, 0.13+/-0.17, P>0.10), but the heritability for LDL cholesterol (LDL-C) was higher (P<0.05) in men than in women (men, 0.79+/-0.21, P<0.01; women, 0.39+/-0.12, P<0.01). The top 14 SNPs that passed the false discovery rate threshold in the families were then tested for replication in an independent population-based sample of 1,750 Afro-Caribbean men aged 40+ years. Our results revealed significant associations for three SNPs in two genes (rs5929 and rs6511720 in LDLR and rs7517090 in PCSK9) and LDL-C in both the family study and in the replication study. Our findings suggest that LDLR and PCSK9 variants may contribute to a variation in LDL-C among African ancestry individuals. Future sequencing and functional studies of these loci may advance our understanding of genetic factors contributing to LDL-C in African ancestry populations.

Association of a common G6PC2 variant with fasting plasma glucose levels in non-diabetic individuals.

BACKGROUND/AIMS: Fasting plasma glucose (FPG) levels correlate with cardiovascular disease and mortality in both diabetic and non-diabetic subjects. G6PC2 encodes a pancreatic islet-specific glucose-6-phosphatase-related protein and G6pc2-null mice were reported to exhibit decreased blood glucose levels. Two recent genome-wide association studies have implicated a role for G6PC2 in regulation of FPGlevels in the general European population and reported the strongest association with the rs560887 SNP. The purpose of this study was to replicate this association in our independent epidemiological samples. METHODS: DNA samples from non-Hispanic white Americans (NHWs; n = 623), Hispanic Americans (n = 410) and black Africans (n = 787) were genotyped for rs560887 using TaqMan allelic discrimination. RESULTS: While no minor allele A of rs560887 was observed among blacks, its frequency was 33% in NHWs and 17.5% in Hispanics. The rs560887 minor allele was associated with reduced FPG levels in non-diabetic NHWs (p = 0.002 under an additive model). A similar trend of association was observed in non-diabetic Hispanics (p = 0.076 under a dominant model), which was more pronounced in normoglycemic subjects (p = 0.036). CONCLUSIONS: Our results independently confirm the robust association of G6PC2/rs560887 with FPG levels in non-diabetic NHWs. The observed evidence for association in Hispanics warrants further studies in larger samples.

Which obesity index is a better predictor for cardiometabolic risk factors in a young adult rural population of Telangana State, India?

BACKGROUND: Waist-to-height ratio (WHtR) has recently been found to be a useful marker of cardiovascular disease (CVD) risk in populations in developed countries; the comparison of various obesity indices, particularly WHtR, has received little study in India and other developing countries. AIM: This study aimed to compare the associations of common obesity indices, body mass index (BMI), waist circumference, waist-hip ratio (WHR), and WHtR, with cardiometabolic risk factors in a young, rural Indian population. SUBJECTS AND METHODS: Anthropometric measurements and cardiometabolic risk factors (hypertension, diabetes, and dyslipidemia) were measured using standardized protocols at the baseline visit of the Longitudinal Indian Family hEalth Pilot Study, a population-based cohort study of child-bearing age women and their husbands in rural Telangana, India. RESULTS: In comparison with most previously studied populations, this population sample (642 males and 980 females) was younger; had lower BMI; and lower rates of diabetes, hypertension, and abnormal lipids (exception of high rates of low high-density lipoprotein). With regard to each of the cardiometabolic risk factors, the associations across the obesity indices tended to be significant, but weak, and similar to each other, whereas the association with WHR was less strong. CONCLUSION: Although WHtR was not a better predictor of cardiometabolic risk than conventional obesity indices, in this young adult Indian population, it was equally good. This raises the prospect of using WHtR as an alternative to BMI for assessing cardiometabolic risk in Indians considering the ease with which it can be easily done and interpreted.

Serum Vitamin D and Age-Related Muscle Loss in Afro-Caribbean Men: The Importance of Age and Diabetic Status.

BACKGROUND: Prospective studies examining the potential association of vitamin D with age-related muscle loss have shown inconsistent results. OBJECTIVE: To examine the association between baseline serum 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)2D), and prospective change in lean mass with aging in African ancestry population. We also determined if associations were modulated by age and diabetes mellitus (DM). DESIGN: Prospective observational cohort study. SETTING: Data were collected from a random sub-sample of 574 men, participants of the Tobago Bone Health Study (TBHS). PARTICIPANTS: 574 Afro-Caribbean men, aged 43+ years (mean age: 59.1 ± 10.5), who were randomly selected as the participants in both the baseline and the follow-up visits. MEASUREMENTS: Baseline fasting serum 25(OH)D was measured using liquid chromatography mass spectrometry (LC-MS/MS), and and 1,25(OH)2D was measured using radioimmunosassay (RIA). Changes in dual-energy X-ray absorptiometry (DXA)-measured appendicular lean mass (ALM), and total body lean mass (TBLM) were measured over an average of 6.0 ± 0.5 years. The associations of 25(OH)D and 1,25(OH)2D with ALM and TBLM were assessed by multiple linear regression model after adjusting for potential confounders. RESULTS: When stratifying all men into two groups by age, greater baseline 25(OH)D and 1,25(OH)2D levels were associated with smaller losses of ALM and TBLM in older (age 60+ years) but not in younger (age 43 - 59 years) men. When stratifying by DM status, the associations of 25(OH)D and 1,25(OH)2D with declines in ALM and TBLM were statistically significant only in prediabetic, but not among normal glycemic or diabetic men. CONCLUSION: Higher endogenous vitamin D concentrations are associated with less lean mass loss with aging among older and prediabetic Afro-Caribbean men independent of potential confounders. Our findings raise a possibility that maintaining high serum vitamin D level might be important for musculoskeletal health in elderly and prediabetic African ancestry men.

Estrogen metabolism and breast cancer risk--a review.

The standard paradigm providing a general mechanistic explanation for the association of cumulative, excessive estrogen exposure and breast cancer risk is that estrogen and perhaps progesterone affect the rate of cell division; and thus manifest their effect on the risk of breast cancer by causing proliferation of breast epithelial cells. Proliferating cells are susceptible to genetic errors during DNA replication which, if uncorrected, can ultimately lead to a malignant phenotype. This standard paradigm has recently been expanded to encompass emerging research data supporting a complementary genotoxic pathway mediated by the generation and redox cycling of reactive oxygen species through the metabolic effects of estrogen metabolites such 4- and 16a-hydroxy catechols. This paradigm shift is necessitated by evidence of estrogen-induced carcinogenesis in several animal and human models following exposure to these estrogen metabolites. This review examines some of the available evidence relating these estrogen metabolites to animal and human breast carcinogenesis.

Case-control study of risk factors for breast cancer in Nigerian women: a pilot study.

OBJECTIVE: To evaluate the risk factors for breast cancer among women in Midwestern and Southeastern Nigeria. DESIGN: A case control study. SETTING: University of Benin Teaching hospital, Benin City and University of Port Harcourt Teaching Hospital, Port Harcourt in Nigeria. SUBJECTS: Fifty one women with diagnosis of breast cancer and their age- and sex matched controls were included in the study. INTERVENTIONS: Data was collected during a 30 minute period after obtaining written informed consent using interviewer-administered questionnaires. RESULTS: Parity > 4 (OR = 0.50, 95% Cl 0.17, 1.46) and duration of breast feeding > 60 months (OR = 0.58, 95% Cl 0.23, 1.48) were associated with reduced risk of breast cancer while birth order > 3 (OR = I.50, 95% Cl 0.25, 8.98), age at first full term pregnancy>20 years (OR = 2.50, 95% Cl 0.78, 7.97) and longer duration of reproductive period (OR = 1.25, 95% Cl 0.34, 4.66) were associated with increased risk of breast cancer. CONCLUSION: The study has shown that high parity and long duration of breastfeeding are associated with reduced risk while high birth order and late age at first full-term pregnancy are associated with increased risk of breast cancer.

Predictors of microalbuminuria in individuals with IDDM. Pittsburgh Epidemiology of Diabetes Complications Study.

OBJECTIVE: To examine the relationships between microalbuminuria and the development of overt diabetic nephrology, elevated blood pressure, and a more atherogenic lipid profile; and to identify risk factors for the development of microalbuminuria in individuals with IDDM. Microalbuminuria has been associated with the subsequent development of overt diabetic nephropathy in individuals with IDDM. It is associated with elevated blood pressure and a more atherogenic lipid profile, but the temporal relationship between the development of microalbuminuria and the changes in these factors is unclear. RESEARCH DESIGN AND METHODS: Baseline characteristics were examined in 256 individuals with IDDM who had normal albumin excretion (urinary AER < or = 20 micrograms/min in > or = 2 timed urine collections) and were re-examined 2 yr later. RESULTS: At follow-up, 24 had developed microalbuminuria (AER 20-200 micrograms/min in > or = 2 timed urine collections) and 1 had developed overt nephropathy (AER > 200 micrograms/min). Overall, the significant independent predictors of microalbuminuria were HbA1 (P < 0.001), low-density lipoprotein (P < 0.01), duration of IDDM (P < 0.05), and systolic blood pressure (P = 0.05). Sex-specific analyses showed HbA1, age, and baseline AER were particularly important for men; whereas, for women, the main predictors were duration of IDDM and triglycerides. Duration-specific analyses showed that HbA1 was an important predictor both for individuals with < and > 20-yr duration. Low-density lipoprotein cholesterol was more important for subjects with shorter durations; whereas triglycerides were important for those with longer durations. CONCLUSIONS: These results suggest that glycemic control, age or duration of IDDM, disturbed lipids, and possibly elevated blood pressure all may contribute to the development of microalbuminuria; and, further, that the adverse cardiovascular risk profile seen in individuals with overt nephropathy may begin to develop even before the detection of microalbuminuria.

Epidemiological risk factors for breast cancer--a review.

The rising global incidence, morbidity and mortality from breast cancer has led to intensified efforts in the search for etiological factors of the disease. While international variations in the incidence of the disease may implicate a role for environmental factors, available evidence indicates that lifetime estrogen exposure may be a critical factor in breast carcinogenesis. While increasing age and the female sex are well-recognized risk factors, reproductive characteristics such as age at menarche and menopause, menstrual irregularity, age at first and last childbirth, parity and breastfeeding have also been linked to breast carcinogenesis. Early menarche and late menopause are associated with increased lifetime exposure to estrogens. In addition, a long period from Tanner stage breast-2 to onset of ovulatory cycles and a long period of luteal inadequacy and anovulatory cycles characteristic of the perimenopausal years creates long estrogen windows favorable for tumor induction. The intense differentiation of the terminal duct lobular unit associated with each full term pregnancy and release of various hormones, autocrine and paracrine growth factors during lactation may explain the protective effects of early age at first full term pregnancy, parity and lactation of breast cancer risk. A protective role for xenoestrogens has been postulated and evidence is emerging in support of an increased breast cancer risk with abortion and prolonged use of postmenopausal hormone replacement therapy. Appreciating relevant risk factors for breast cancer in the population is central to any preventive and control program aimed at reducing the burden of the disease through the design and implementation of culturally sensitive interventions.

Weight threshold and blood pressure in a lean black population.

Hypertension is virtually absent in very lean rural African populations but is becoming more common in higher-weight urban African populations and is very common in predominantly obese Westernized black populations. This implies that there is a threshold above which weight is related to blood pressure. We studied urban Nigerian civil servants, a lean population in transition toward a more Westernized lifestyle. Blood pressure, fat-related measurements, fasting insulin, physical activity, alcohol intake, macronutrient intake, and electrolyte excretion were measured in 500 male and 299 female civil servants in Benin City, Nigeria, in 1992. Median body mass index (BMI) was 21.5 kg/m2 in men and 24.0 kg/m2 in women. Examination of age-adjusted mean blood pressure across quantiles of BMI in men and women suggested a threshold of 21.5 kg/m2 below which blood pressure was not correlated with BMI. Above this threshold blood pressure was correlated with BMI. Comparison of groups above and below the lower BMI threshold found that differences in blood pressure-BMI covariation were not explained by differences in alcohol intake, caloric or macronutrient intake, or electrolyte excretion. Physical activity was higher in men below the threshold. Fasting insulin and waist-hip ratio were strongly correlated with BMI even in this very lean population but neither was independently related to blood pressure. We conclude that there is a threshold below which little relationship between blood pressure and weight is observed. Above this threshold even at levels considered lean in US blacks, weight is a major determinant of blood pressure in this population of African blacks, which shares ancestry with US blacks.

Correlates of serum lipids in a lean black population.

Exposure to an urban, sedentary work environment and higher socioeconomic status (SES) may stimulate adoption of Westernized lifestyles by populations in developing countries reversing the historically low risk for coronary heart disease. In a study of serum lipids in 1407 Nigerian civil servants, aged 25-54 years, we found a more atherogenic lipid profile among higher SES males and females compared with lower SES (LDL-cholesterol, 113 vs. 97 mg/dl, males, 125 vs. 114 mg/dl, females). Mean body mass index (BMI, kg/m2) in higher and lower SES was 22.6 and 21.3, respectively, males, and 24.7 and 24.4, respectively females. A strong relationship was observed between BMI and lipids although this relationship was absent among the leanest half of the population (BMI < 21.8). In multiple regression, SES and BMI were both strong and independent predictors of cholesterol. Both high and low SES consumed a typical Nigerian low fat, high carbohydrate diet, but somewhat higher meat, milk and egg intake suggested that some Westernization of the diet had occurred among the higher SES. Physical activity was lower among the higher SES. We conclude that SES related changes in lifestyle contribute to substantially higher total and LDL-cholesterol even in a generally lean population consuming a low fat diet.

Racial differences in the distribution of a low density lipoprotein receptor-related protein (LRP) polymorphism and its association with serum lipoprotein, lipid and apolipoprotein levels.

The low density lipoprotein (LDL) receptor-related protein (LRP) is a cell receptor that has close structural homology to the LDL and very low density lipoprotein receptors and thus is believed to play an important role in lipid metabolism. This study was carried out to evaluate the distribution of a known tetranucleotide repeat polymorphism in the LRP gene and its association with serum lipoprotein-lipid and apolipoprotein levels in four large samples comprising Hispanics (n=373) and non-Hispanic Whites (n=522) from the U.S. and Nigerian Blacks from Sokoto (n=390) and Benin (n=800). A total of four alleles, designated 83, 87, 91 and 95 bp, were observed. The 83 bp allele was observed at 0.4-1.1% in the two U.S. populations but was completely absent in African Blacks. Sokoto Blacks had significantly different frequencies of the 87 and 91 bp alleles compared to Hispanics (P=0.008) and non-Hispanic Whites (P=0.024). The frequency of the 91 bp allele was also significantly higher in Benin Blacks compared to Hispanics (P=0.026) and non-Hispanic Whites (P=0.054). The analysis of the relationship between the LRP polymorphism and serum lipid traits yielded some significant race and gender specific significant association for lipoprotein(a) in non-Hispanic White males (P=0.02); HDL2-cholesterol in Hispanic females (P=0.03) and apolipoprotein B in Benin males (P=0.04). We also observed an interaction between the LRP polymorphism and menopausal status for Lp(a) in Hispanic females (P=0.014). However, considering multiple comparisons were performed, these associations could be due to chance. Our data indicate that although the LRP tetranucleotide polymorphism exhibits inter-racial differences in its distribution, it does not appear to have a significant role in affecting serum lipid traits.

Red blood cell sodium-lithium countertransport and cardiovascular risk factors in black and white college students.

Whites with essential hypertension have high activity of cell membrane sodium-lithium (Na+-Li+) countertransport when compared with normotensives. To determine whether elevated Na+-Li+ countertransport is related to the twofold higher risk of hypertension in US blacks, maximal rates of red blood cell (RBC) Na+-Li+ countertransport were measured in 34 black and 21 white male college students. The race groups were similar in social and physical measurements. Mean Na+-Li+ countertransport activity (mmol Li/RBC per h) was significantly lower in blacks than in whites (0.214 +/- 0.083 versus 0.295 +/- 0.083, P less than 0.001). Countertransport activity was positively correlated with Type A behaviour among whites (r = 0.45, P = 0.039). Other within race correlations between Na+-Li+ countertransport activity and blood pressure and cardiovascular risk factors were generally positive though not significant in whites, whereas they were small or negative in blacks. If Na+-Li+ countertransport has a role in the aetiology of hypertension, it would appear to differ between blacks and whites.

The role of socioeconomic status and serum fatty acids in the relationship between intake of animal foods and cardiovascular risk factors.

Little is known regarding the relationship of serum fatty acids to cardiovascular risk factors in Nigerian populations. Civil servants with higher socioeconomic status (SES) in Nigeria appear to be in cultural transition toward a more Westernized lifestyle. For this study the food intakes of 397 civil servants were estimated from two 24-h recalls. Fatty acids in serum total lipids were measured in both absolute weight concentration and percentage composition. Daily meat intake was 43.5 g, and fish intake was 70.5 g. The intakes of meat, eggs, and milk were higher in high SES Nigerians than in low SES Nigerians. The concentration of total fatty acids (TFA, the sum of 12 serum fatty acids) was also higher in high SES men and women, as compared with low SES men and women (2064, 2060, 1831, and 1776 mg/L, respectively). There were significant direct associations between meat intake and serum level of arachidonic acid, and between fish intake and serum levels of eicosapentaenoic acid and docosahexaenoic acid. TFA was positively associated with cholesterol, low-density-lipoprotein cholesterol (LDLc), and triglycerides across gender and SES groups after adjustment for body mass index, fasting insulin level, and age. Nigerian women were compared with two groups of American women. We concluded that fatty acids in absolute weight concentration reflected the amount of fat intake. The level of TFA was directly related to cardiovascular risk factors in Nigerians. Follow-up of such populations in cultural transition can facilitate the understanding of the true roles of animal food intake in the early evolution of atherosclerosis.

Adequacy of a single visit for classification of hypertensive status in a Nigerian civil servant population.

BACKGROUND: Concern has been expressed regarding the adequacy of classifying individuals as hypertensive based upon a single blood pressure determination and/or the average of readings taken at a single visit and the appropriateness of these determinations in cross-cultural comparisons of rates of hypertension. METHODS: This analysis investigated the potential classification variability by comparing hypertensive status determined by 1) a single reading, 2) an average of the second and third determination at the first visit, and 3) an average of the second and third determinations obtained at each of three visits according to a standardized protocol. Kappa statistic, sensitivity and specificity were calculated to assess the agreement of hypertension classification for 804 subjects in the Health Survey in Nigerian Civil Servants, Benin City, 1992. Data were also compared to other published studies for variability in hypertension classification with repeated blood pressure determinations. RESULTS: Good to excellent agreement was observed for the entire population between the single blood pressure determination, the average of the first visit, and the average of three visits. Sensitivity and specificity measures were also acceptable for the entire population. Further analysis by sex and staff status (a measure of socioeconomic status) found no apparent distinctions between the groups. CONCLUSION: Contrasting the data with other published studies, conducted in both developed and developing countries, we note no greater variability in repeated blood pressure measurements, and conclude that the average of blood pressure determinations at a single visit in this working urban population is adequate for determining hypertensive status for comparisons with hypertension rates in Westernized populations.