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Biomedical subjects

R S Cooper

Publications and source records attributed to R S Cooper.

At least 19 recordsLinked to original sources

The effect of genetic variation in angiotensinogen on serum levels and blood pressure: a comparison of Nigerians and US blacks.

Molecular variants of angiotensinogen (AGT) have been associated with AGT level and hypertension (HT). However, results from reported studies vary considerably between- and within-studied populations. We performed association analysis of AGT gene variants with AGT levels and HT in samples of African descent families, including 595 Nigerians and 901 African Americans. We evaluated association using haplotypes defined by a set of single-nucleotide polymorphisms selected from a previous detailed study of the gene haplotype structure. In the sample of Nigerian families, AGT haplotype H1 was associated with high plasma level. Results were not significant for blood pressure (BP) or HT. For the African-American population, we found significant association between low plasma AGT level and haplotype H7. Furthermore, we found weak associations of H1 with hypertensive status and H7 with low systolic BP. However, no significant association between H1 and high plasma level was found. We conclude that the two distantly related haplotypes, H1 and H7, are associated, but have opposite effects on the phenotypes in two populations of African origin.

Adult↗

A randomized trial on sodium reduction in two developing countries.

Hypertension remains the most common cardiovascular risk factor in developing countries, yet the majority of patients have no access to pharmacological therapy. Population-wide preventive strategies, such as salt restriction, are an attractive alternative, but experience in resource-poor settings is limited. To address this question, we conducted a randomized crossover study of salt restriction in adults living in Nigeria and Jamaica in order to estimate the mean blood pressure (BP) response. After a 4-week run-in period to determine willingness to adhere to a low-salt diet, 56 Jamaicans and 58 Nigerians completed an 8-week crossover study of low-salt and high-salt intake. Baseline BPs were in the normotensive range (systolic=125 mmHg in Jamaica, 114 mmHg in Nigeria). Baseline urinary sodium excretion was 86.8 and 125.6 mEq/day in Nigeria and Jamaica, respectively. The mean difference between urinary sodium excretion at baseline and at the end of the 3-week low-sodium phase was 33.6 mEq/day in Nigeria and 57.5 mEq/day in Jamaica. During the high-sodium phase, mean change in urinary sodium excretion from baseline to week 3 was 35.0 and 5.5 mEq/day in Nigeria and Jamaica, respectively. The mean change in systolic BP ('high' vs 'low' sodium phase) was approximately 5 mmHg in both groups. This study suggests that the efficacy of sodium reduction in developing countries equals those noted in more affluent cultures. If promoted on a wide scale, sodium reduction could be used to treat persons with established hypertension, and more importantly, to prevent age-related increases in BP in poor communities.

Adult↗

Relationship between blood pressure and physical activity assessed with stable isotopes.

Intrapopulation and interpopulation variation in blood pressure (BP) often reflects the joint effect of a complex set of risk factors, including lifestyle factors such as physical activity, diet, smoking and alcohol use. In this study, we set out to quantify the impact of habitual levels of physical activity on BP within and between three populations at contrasting levels of population risk of hypertension. Individuals were randomly sampled from communities in Nigeria (n=57), Jamaica (from Kingston, n=35) and the United States (from the Chicago area, n=32). Activity energy expenditure (AEE) (estimated from resting energy expenditure measured by indirect calorimetry and total expenditure measured with doubly labelled water) was used as an objective estimate of physical activity. In each of the three samples, there was a consistent negative correlation between BP and AEE. This negative association persisted after adjustment for age, sex and body fat (body mass index or percent fat mass). In multivariate models, adiposity was no longer a significant predictor of BP after accounting for low AEE. In conclusion these data suggest that habitual levels of physical activity may have a generalizable relationship with BP in populations with widely different social and environmental characteristics.

Adult↗

SNP haplotypes in the angiotensin I-converting enzyme (ACE) gene: analysis of Nigerian family data using gamete competition models.

Gamete competition models were used to explore the relationships between 13 ACE gene polymorphisms and plasma ACE concentration in a set of Nigerian families. Several markers in the 5' and 3' regions of the gene were significantly associated with ACE concentration (P < 10(-4)). Multi-locus genotypes comprising different combinations of markers from the 5' UTR and the 3' region of the gene were also analysed; in addition to G2350A, in the 3' region, two markers from the 5' UTR (A-5466C and A-240T) were found to be associated with ACE concentration. These results are consistent with reports that have suggested the presence of at least two ACE-linked QTLs, and demonstrate the utility of gamete competition models in the exploratory investigation of the relationship between a quantitative trait and multiple variants in a small genomic region.

Adult↗

Energetic determinants of glucose tolerance status in Jamaican adults.

As type 2 diabetes mellitus (DM2), obesity and sedentary lifestyles are increasing in developing countries, this observational study investigated the role of physical activity on DM2 in Jamaica. Anthropometry, body composition (by bioelectrical impedance analysis) and glucose tolerance status was assessed in 722 adults in 1993 and 1997. Energy expenditure was estimated in a subset using measured resting energy expenditure in combination with self-reported activity recalls. The rates of impaired glucose tolerance (IGT) were 23.7 and 27.3%, and DM2 were 16.3 and 23.7% among men and women, respectively. After adjusting for body composition, a one-unit increase in physical activity significantly reduced the odds of having diabetes (OR = 0.05; 95% CI: 0.004, 0.66), but not IGT. Hence, decreased physical activity is a significant independent contributor to the high rates of glucose intolerance in Jamaica. Efforts must be directed at minimizing obesity and increasing physical activity in developing countries.

Adult↗

Higher income is more strongly associated with obesity than with obesity-related metabolic disorders in Jamaican adults.

OBJECTIVE: This study compares how income is related to obesity vs two obesity-related cardiovascular disease (CVD) risk factors-diabetes and hypertension-in adults from Jamaica. DESIGN: A cross-sectional population-based survey was used. In total, 847 men and 1249 women aged 25-74 y were randomly recruited from a periurban area in 1993-1998. MEASUREMENTS: Trained interviewers measured anthropometry and blood pressure, obtained fasting blood and collected self-reported data on income and disease history. RESULTS: Income was strongly and positively associated with obesity in men. In women, obesity levels were high even among the very poor, and the income gradient was more moderate. Although obesity-and particularly central fatness-was strongly associated with diabetes and hypertension prevalence, income was not significantly related to these disorders. CONCLUSIONS: Future research in developing countries should independently explore associations between income and obesity vs obesity-related disorders, and identify factors that explain any disparities.

Adult↗

Features of isolated post-challenge hyperglycaemia in Jamaican adults.

Isolated post-challenge hyperglycaemia (IPH) can be defined as a two-hour plasma glucose concentration > or = 11.1 mmol/L with a fasting plasma glucose concentration < 7.0 mmol/L. The aim of this prospective study was to determine the prevalence of IPH in a cohort of Jamaican individuals, and to determine if simple clinical features may predict the presence and subsequent diagnosis of IPH. A cohort of 1694 adults aged 25-74 years without physician-diagnosed diabetes mellitus was randomly selected. An oral glucose tolerance test (OGTT) was performed. Anthropometry, blood pressure and lipid profiles were measured. The prevalence of undiagnosed diabetes mellitus by the 1999 World Health Organization criteria was 6.4%. IPH accounted for 24% of these cases and 1.4% of the entire population. Individuals with IPH were significantly older, with greater body mass index, waist-hip ratio, systolic blood pressure, fasting blood glucose, total cholesterol and LDL-cholesterol than individuals with normal glucose tolerance. Individuals with IPH were not significantly different from individuals with fasting plasma glucose levels > or = 7 mmol/L (i.e. fasting hyperglycaemia) in anthropometry or blood pressure. However, total cholesterol and LDL-C were significantly elevated in the IPH group. OGTT screening of individuals with impaired fasting glucose (i.e. 6.1-6.9 mmol/l) could reduce the IPH group by 50%. Reducing the threshold for fasting glucose to 5.6 mmol/L would correctly classify 87% of the population. We concluded that individuals with IPH have features of the metabolic syndrome, which can aid in selection for screening. OGTT screening of individuals with fasting glucose values of 5.6-6.9 mmol/l is needed to identify IPH.

Adult↗

Commentary: considerations for use of racial/ethnic classification in etiologic research.

Numerous authors have critiqued the use of race as an etiologic quantity in medical research. Despite this criticism, the use of variables encoding racial/ethnic categorization has increased in epidemiology, and most researchers agree that important variation in disease risk is captured by this classification system. Previous discussions have generally neglected to articulate guidelines for appropriate use of racial/ethnic information in etiologic research. The authors summarize the logical, conceptual, and practical problems associated with the "ethnic paradigm" as currently applied in biomedical sciences and offer a set of methodological recommendations toward more valid use of racial/ethnic classification in etiologic studies. These suggested guidelines address issues of variable definition, study design, and covariate control, providing a consistent foundation for etiologic research programs that neither ignore racial/ethnic disease disparities nor obfuscate the nature of these disparities through inappropriate analytical approaches. This methodological analysis of racial/ethnic classification as an epidemiologic quantity provides a formal basis for a focus on racism (i.e., social relations) rather than race (i.e., innate biologic predisposition) in the interpretation of racial/ethnic "effects."

Causality↗

Linkage and association analysis of angiotensin I-converting enzyme (ACE)-gene polymorphisms with ACE concentration and blood pressure.

Considerable effort has been expended to determine whether the gene for angiotensin I-converting enzyme (ACE) confers susceptibility to cardiovascular disease. In this study, we genotyped 13 polymorphisms in the ACE gene in 1,343 Nigerians from 332 families. To localize the genetic effect, we first performed linkage and association analysis of all the markers with ACE concentration. In multipoint variance-component analysis, this region was strongly linked to ACE concentration (maximum LOD score 7.5). Likewise, most of the polymorphisms in the ACE gene were significantly associated with ACE (P<.0013). The two most highly associated polymorphisms, ACE4 and ACE8, accounted for 6% and 19% of the variance in ACE, respectively. A two-locus additive model with an additive x additive interaction of these polymorphisms explained most of the ACE variation associated with this region. We next analyzed the relationship between these two polymorphisms (ACE4 and ACE8) and blood pressure (BP). Although no evidence of linkage was detected, significant association was found for both systolic and diastolic BP when a two-locus additive model developed for ACE concentration was used. Further analyses demonstrated that an epistasis model provided the best fit to the BP variation. In conclusion, we found that the two polymorphisms explaining the greatest variation in ACE concentration are significantly associated with BP, through interaction, in this African population sample. Our study also demonstrates that greater statistical power can be anticipated with association analysis versus linkage, when markers in strong linkage disequilibrium with a trait locus have been identified. Furthermore, allelic interaction may play an important role in the dissection of complex traits such as BP.

Adult↗

Distribution and functional consequences of nucleotide polymorphisms in the 3'-untranslated region of the human Sep15 gene.

Selenium has been shown to prevent cancer in a variety of animal model systems. Both epidemiological studies and supplementation trials have supported its efficacy in humans. However, the mechanism by which selenium suppresses tumor development remains unknown. Selenium is present in known human selenoproteins as the amino acid selenocysteine (Sec). Sec is inserted cotranslationally in response to UGA codons within selenoprotein mRNAs in a process requiring a sequence within the 3'-untranslated region (UTR), referred to as a Sec insertion sequence (SECIS) element. Recently, a human Mr 15,000 selenoprotein (Sep15) was identified that contains an in-frame UGA codon and a SECIS element in the 3'-UTR. Examination of the available cDNA sequences for this protein revealed two polymorphisms located at position 811 (C/T) and at position 1125 (G/A) located within the 3'-UTR. Here, we demonstrate significant differences in Sep15 allele frequencies by ethnicity and that the identity of the nucleotides at the polymorphic sites influences SECIS function in a selenium-dependent manner. This, together with genetic data indicating loss of heterozygosity at the Sep15 locus in certain human tumor types, suggests that Sep15 may be involved in cancer development, risk, or both.

3' Untranslated Regions↗

Localization of the Q1 mutation by cladistic analysis.

The completion of the human genome project appears to be in sight and enormous new information resources will be available. The challenge now facing the scientific community is to use this information. In this paper, we applied cladistic analysis to the sequenced data in a Genetic Analysis Workshop 12 simulation problem. The Q1 mutation was localized to a 5-kb segment, in which the true mutation is located. Our analysis shows that cladistic analysis, which summarizes evolutionary history, can be a powerful tool in gene mapping.

Alleles↗

Racial differences and the genetics of hypertension.

Variation in the prevalence of hypertension among human populations has been used to examine a wide range of research questions. The best known example has always been the twofold greater prevalence among blacks, which has provoked a debate about the relative importance of environmental and genetic factors. This problem is complicated because it requires an understanding of both the genetics of hypertension and the genetic basis of variation among populations. Molecular data accumulated over the past year are beginning to provide new insights into this old question. Modest progress has now been made in the genetics of hypertension. Important advances have been made in understanding rare hypertension syndromes, and large-scale studies of the general population are under way, although the results to date are inconclusive. Markers used to search for hypertension genes can also provide estimates of between-population variability. These data, which are based on genetic variants used for etiologic research, confirm previous evidence of group-specific variation, while underscoring the limited magnitude of this variation. Despite rapid progress, this work is still in its infancy and raises more questions than it answers.

Black People↗

Height and risk of fatal prostate cancer: findings from the National Health Interview Survey (1986 to 1994).

PURPOSE: Height is determined by genetic and nutritional factors mediated through the endocrine system early in life and, thus, may be related to subsequent risk of fatal prostate cancer. This hypothesis was examined in a large representative U.S. national sample. METHODS: Data from the National Health Interview Survey (NHIS) were analyzed to determine whether height was prospectively related to the risk of fatal prostate cancer in 110,042 men age > or = 50 years old interviewed between 1986 and 1994. Height was self-reported and vital status and causes of death ascertained using the National Death Index. Endpoints were deaths that listed prostate cancer as the underlying cause and deaths with any mention of prostate cancer. Relative risks (RR) and their 95% confidence intervals (CI) were calculated using Cox proportional hazards models adjusted for age, race, weight, and education. RESULTS: Six hundred and thirty-three deaths listing of prostate cancer as the underlying cause and 910 deaths with any mention of prostate cancer were identified. Height was associated neither with risk of death with prostate cancer listed as the underlying cause nor with risk of death with any mention of prostate cancer (multivariate p for trend = 0.1318 and 0.0698, respectively). Risks were marginally greater among the tallest men compared to the shortest (< or = 171.4 vs. > or = 182.9 cm), but not significantly (RR = 1.21, 95% CI = 0.92 to 1.57, and RR = 1.24, 95% CI = 0.98 to 1.58 for 'underlying cause' and 'any mention', respectively). CONCLUSIONS: Height alone was not related to risk of fatal prostate cancer in this population.

Body Height↗

The beta 3-adrenergic receptor gene and obesity in a population sample of African Americans.

OBJECTIVE: To examine the role of the Trp64Arg polymorphism in the beta 3-adrenergic receptor gene and the beta 3-adrenergic receptor gene locus in obesity-related traits in African Americans. SUBJECTS: A total of 687 individuals representing 193 African American families who were residents of metropolitan Chicago. MEASUREMENTS: Genotyping of the Trp64Arg polymorphism in the beta 3-adrenergic receptor gene and three microsatellite markers flanking the beta 3-adrenergic receptor gene (ADRB3) locus and measuring various obesity-related traits, including body mass index (BMI), fat-free mass, fat mass, percentage fat mass, waist circumference and serum lipid levels. RESULTS: The prevalence of obesity (defined as body mass index > or = 30 kg/m(2)) in the population was 27.3% and 51.2% in men and women, respectively. The frequency of the Arg64 allele was 10.0%. Multivariate regression analyses confirmed the existence of a significant contribution of familial variance to each of the five obesity-related traits noted above. Likelihood ratio statistics computed in a multivariate regression analysis failed to demonstrate a significant association between the Arg64 allele and any of the five obesity-related traits. Single and multipoint analyses using extended Haseman--Elston regression analyses failed to demonstrate suggestive evidence of linkage of three microsatellite markers that flank the beta 3-adrenergic receptor gene to BMI, percentage body fat, waist circumference or serum leptin levels. CONCLUSION: Given the contribution of familial variance to obesity-related traits in this population, neither the null finding for the Arg64 allele nor the lack of evidence of linkage of the ADRB3 locus to obesity-related traits could be attributed to lack of transmissibility of the traits suggesting that neither the Arg64 variant of the beta 3-adrenergic receptor gene nor another genetic variant in or near the ADRB3 locus contribute significantly to familial aggregation of obesity-related traits in African Americans. International Journal of Obesity (2001) 25, 54-60

Adipose Tissue↗

Heritability of obesity-related traits among Nigerians, Jamaicans and US black people.

OBJECTIVE: The mean values for anthropometric traits vary across population groups and this variation is clearly determined for the most part by the environment. The familiarity of anthropometric traits also varies in reports from different populations, although this variation has not been shown to follow a consistent pattern. To examine whether heritability is influenced by socio-cultural factors, we conducted a cross-cultural study of populations of the African diaspora. PARTICIPANTS: Data were collected on 1868 family members from Nigeria, 623 from Jamaica and 2132 from metropolitan Chicago, IL, USA. MEASUREMENTS: Height and weight were measured and body mass index (kg/m(2)) calculated. Fat-free mass, fat mass and percentage body fat were estimated using bioelectrical impedance analysis. Plasma leptin concentrations were also measured. The proportion of variance attributable to additive genetic and non-shared environmental components was estimated with the maximum likelihood variance decomposition method. RESULTS: Mean values for all anthropometric traits increased along the socio-cultural gradient, and obesity increased from 5% in Nigeria to 23% in Jamaica and 39% in the USA. Within populations the relationships among traits both within individuals and within families were highly consistent. Heritability estimates for weight, body mass index, fat mass and percentage body fat were approximately 50% for all groups. Heritability for height was lower in Nigeria (62%) than in Jamaica (74%) or the US (87%). CONCLUSION: The familial patterns of body size and energy storage appear to be consistent in these genetically related populations across a wide range of environmental conditions.

Adult↗

Recent changes in the health status of the older U.S. population: findings from the 1984 and 1994 supplement on aging.

OBJECTIVES: To examine the changes in the use of health care services, physical functioning, disability, and other aspects of health status in the older U.S. population between 1984 and 1994. DESIGN AND SETTING: The 1984 and 1994 National Health Interview Survey Supplements on Aging, which were national probability samples of the civilian, noninstitutionalized population age 70 and older. PARTICIPANTS: A total of 7,541 and 9,447 persons, representing the 17.3 million and 21.8 million U.S. population age 70 and older in 1984 and 1994, respectively. MEASUREMENTS: Annual bed-limitation days, doctor visits, episodes and days of hospital stays, limitation in 10 measures of physical performance, disability in seven activities of daily living (ADLs) and six instrumental activities of daily living (IADLs), and participation in social activities and exercise. RESULTS: The annual bed-limitation days and hospital stays declined significantly in both men and women between 1984 and 1994. There was a large decrease in the prevalence of limitation in physical performance and a smaller decrease in disability of IADLs. The changes were greater in women than in men. The prevalence of disability in ADLs was not changed in women in general and increased somewhat in men. Significant increases in the proportion of persons participating in certain social activities and regular exercise were found in both men and women. Jointly considering the indicators, including annual bed days and hospital stays, physical performance, ADLs, and IADLs, 4.2% more men and 3.1% more women were physically robust in 1994 than in 1984. Approximately 420,000 more older people would have lived in a severely restricted and disabled state in 1994 if the rate of limitation had not declined. CONCLUSION: This study provides evidence of an overall improvement in the health status of older Americans but inconsistency in the trends existed for different disability measures and for population subgroups.

Activities of Daily Living↗

Social inequality, ethnicity and cardiovascular disease.

BACKGROUND: Epidemiological research on cardiovascular risk factors has led to important advances in prevention science by providing insights that have now resulted in substantial reductions in mortality. This research used the variation in risk among individuals as the guide to causal exposures. Large differentials remain among socio-demographic groups, however, and the causes of these differentials may be distinctly different from those observed at the individual level. METHODS: Vital statistics and census data from the US and selected regions were used in an ecologic analysis. RESULTS: In 1996 heart disease mortality in the US varied from 156/100 000 among African-American women to 51/100 000 among Asian women; similar differentials were observed for men. Income equality was correlated with heart disease mortality among the 47 largest US cities (r = -0.4; P = 0.006). Independent of income equality, racial segregation was also associated with risk of death from cardiovascular disease in this sample of cities. CONCLUSIONS: Social processes generate marked differentials in heart disease mortality among demographic groups. In the US, death rates are currently 2-3 times higher among African Americans compared to Asians. Broadly speaking, this variation results from their separate cultural legacies, based on well-recognized lifestyle factors and dietary patterns. Ecological comparisons across cities that share similar lifestyle patterns suggest that income inequality and patterns of racial discrimination are each associated with large variation in mortality in a similar manner. Racism and social inequality can be conceptualized as social causes of excess cardiovascular mortality that may not be measurable at the individual level.

Cardiovascular Diseases↗

Nutritional consequences of the African diaspora.

Along with their foods and dietary customs, Africans were carried into diaspora throughout the Americas as a result of the European slave trade. Their descendants represent populations at varying stages of the nutrition transition. West Africans are in the early stage, where undernutrition and nutrient deficiencies are prevalent. Many Caribbean populations represent the middle stages, with undernutrition and obesity coexisting. African-Americans and black populations in the United Kingdom suffer from the consequences of caloric excess and diets high in fat and animal products. Obesity, non-insulin-dependent diabetes mellitus, hypertension, coronary heart disease, and certain cancers all follow an east-to-west gradient of increasing prevalence. Public health efforts must focus not only on eradicating undernutrition in West Africa and the Caribbean but also on preventing obesity, hypercholesterolemia, and their consequences. Fortunately, a coherent and well-supported set of recommendations exists to promote better nutrition. Implementation of it founders primarily as a result of the influence of commercial and political interests.

Africa↗