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Richard Cooper

Publications and source records attributed to Richard Cooper.

At least 37 records · Page 2Linked to original sources

Angiotensin-converting enzyme gene polymorphisms and obesity: an examination of three black populations.

We examined the association between obesity and 13 angiotensin-converting enzyme (ACE) gene polymorphisms, including the presence (I) or absence (D) of an Alu element in intron 16 (I/D polymorphism), and performed haplotype analysis using data collected from participants of a community survey of hypertension among blacks living in Ibadan, Nigeria; Spanish Town, Jamaica; and Chicago, IL. Transmission distortion of ACE gene polymorphisms and haplotypes from heterozygous parents to affected offspring was examined in each study population. To estimate haplotypes, polymorphisms were divided into three groups based on their position on the ACE gene. No ACE gene polymorphism was consistently overtransmitted from parents to obese offspring among the three populations. However, the haplotype ACE1-ACE5 TACAT, located in the promoter region, was significantly overtransmitted from parents to obese offspring in both the U.S. and Nigerian populations. No haplotype was significantly overtransmitted from parents to obese offspring among the Jamaicans. In conclusion, we noted the overtransmission of a particular ACE gene promoter region haplotype from parents to obese offspring in two separate black populations. These data suggest that ACE gene polymorphisms may influence the development of weight gain.

Adult↗

Obesity and prevalent and incident CKD: the Hypertension Detection and Follow-Up Program.

BACKGROUND: Obesity is associated with increased single-nephron glomerular filtration rate, which may increase the risk for chronic kidney disease (CKD), especially when combined with hypertension. However, epidemiological data supporting an association between overweight and obesity and risk for CKD currently are limited. METHODS: We used data from the Hypertension Detection and Follow-Up Program (HDFP) to test the hypothesis that overweight and obesity are associated with incident CKD in 5,897 hypertensive adults. Serum and spot urine samples were collected at baseline and year 5. CKD is defined as the presence of 1+ or greater proteinuria on routine urinalysis and/or an estimated glomerular filtration rate less than 60 mL/min/1.73 m2 (<1.0 mL/s). RESULTS: In HDFP participants without CKD at baseline, the incidence of CKD at year 5 was 28% in the ideal-body-mass-index group, 31% in the overweight group, and 34% in the obese group. After adjustment for all covariates, including diabetes mellitus, mean baseline diastolic blood pressure, and slope of diastolic blood pressure, both baseline overweight (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.05 to 1.41) and obesity (OR, 1.40; 95% CI, 1.20 to 1.63) were associated with increased odds of incident CKD at year 5. Similar results were noted after exclusion of participants with baseline diabetes mellitus, with both overweight (OR, 1.22; 95% CI, 1.05 to 1.43) and obesity (OR, 1.38; 95% CI, 1.17 to 1.63) remaining significantly associated with incident CKD. CONCLUSION: These results suggest that obese adults with hypertension have an increased risk for CKD.

Adult↗

Ethnicity and human genetic linkage maps.

Human genetic linkage maps are based on rates of recombination across the genome. These rates in humans vary by the sex of the parent from whom alleles are inherited, by chromosomal position, and by genomic features, such as GC content and repeat density. We have examined--for the first time, to our knowledge--racial/ethnic differences in genetic maps of humans. We constructed genetic maps based on 353 microsatellite markers in four racial/ethnic groups: whites, African Americans, Mexican Americans, and East Asians (Chinese and Japanese). These maps were generated using 9,291 subjects from 2,900 nuclear families who participated in the National Heart, Lung, and Blood Institute-funded Family Blood Pressure Program, the largest sample used for map construction to date. Although the maps for the different groups are generally similar, we did find regional and genomewide differences across ethnic groups, including a longer genomewide map for African Americans than for other populations. Some of this variation was explained by genotyping artifacts--namely, null alleles (i.e., alleles with null phenotypes) at a number of loci--and by ethnic differences in null-allele frequencies. In particular, null alleles appear to be the likely explanation for the excess map length in African Americans. We also found that nonrandom missing data biases map results. However, we found regions on chromosome 8p and telomeric segments with significant ethnic differences and a suggestive interval on chromosome 12q that were not due to genotype artifacts. The difference on chromosome 8p is likely due to a polymorphic inversion in the region. The results of our investigation have implications for inferences of possible genetic influences on human recombination as well as for future linkage studies, especially those involving populations of nonwhite ethnicity.

Black or African American↗

Association between chronic kidney disease and coronary artery calcification: the Dallas Heart Study.

The hypothesis that chronic kidney disease (CKD) is associated with increased coronary artery calcification (CAC) was tested using data from the Dallas Heart Study, a representative sample of Dallas County residents aged 30 to 65 yr. CKD was defined as presence of microalbuminuria and GFR > or =60 ml/min per 1.73 m(2) (stage 1 to 2), or GFR <60 ml/min per 1.73 m(2) (stage 3 to 5), excluding end-stage kidney disease. Logistic regression was used to examine the association between stages of CKD and CAC scores >10, >100, and >400 versus scores < or =10 compared with no CKD while adjusting for covariates. Analyses were repeated after stratifying by presence of diabetes. The mean age was 43.9 yr, and hypertension and diabetes were noted in 31.0 and 9.8%, respectively. No association was noted between stage 1 to 2 CKD and increased CAC scores. Compared with no CKD, stage 3 to 5 CKD was associated with CAC scores >100 (odds ratio, 2.85; 95% confidence interval, 0.92 to 8.80) and >400 (odds ratio, 8.35; 95% confidence interval, 1.94 to 35.95) in the total population after adjustment for covariates, but these associations were substantially reduced after exclusion of participants with diabetes. Participants with diabetes and stage 3 to 5 CKD had a ninefold increased odds of CAC scores >10 versus scores < or =10 compared with participants with diabetes and without CKD, whereas no association was noted between stage 3 to 5 CKD and CAC scores >10 in the nondiabetic population. In conclusion, stage 3 to 5 CKD is associated with increased CAC scores, but this association may be substantially stronger among adults with diabetes. These findings need to be confirmed in study populations that include adults >65 yr of age and a larger number of CKD cases.

Adult↗

Genome scan for hypertension in nonobese African Americans: the National Heart, Lung, and Blood Institute Family Blood Pressure Program.

BACKGROUND: Obesity is an important risk factor for hypertension, but epidemiologic studies provide evidence for the development of hypertension independent of obesity. In addition, the search for hypertension susceptibility genes should prove more informative when applied to a homogeneous subset of patients, such as those that are not obese. For this reason, we sought to identify genomic regions influencing susceptibility to hypertension in a nonobese sample of hypertensive African American families. METHODS: A genome-wide linkage scan was performed in a sample of 275 African American hypertensive families containing two or more nonobese (body mass index, < or = 30 kg/m2) individuals recruited by Networks of the Family Blood Pressure Program (FBPP). RESULTS: The best evidence for linkage of hypertension among the FBPP African American families was found on chromosome 2 (log of the odds [LOD]= 3.59 at 230 cM). All other chromosomes contained LOD scores less than 2. The African American sibships from the GENOA Network appear to largely contribute to the evidence for linkage on chromosome 2 (LOD = 4.07 at 233 cM). CONCLUSIONS: Significant evidence for linkage to hypertension in nonobese African American families was identified on chromosome 2q. These results suggest the presence of genes influencing susceptibility to adiposity-independent hypertension.

Black or African American↗

Racial/ethnic differences in hypertension and hypertension treatment and control in the multi-ethnic study of atherosclerosis (MESA).

BACKGROUND: Most previous studies investigating the association between ethnicity and hypertension focused on differences between African Americans and whites and did not include other racial/ethnic groups such as Chinese or Hispanics. METHODS: We used data from the Multi-Ethnic Study of Atherosclerosis (MESA), a population-based study of 6814 adults without clinical cardiovascular disease, to examine the association between ethnicity and hypertension and hypertension treatment among white, African American, Chinese, and Hispanic ethnic groups. RESULTS: The prevalence of hypertension, defined as systolic blood pressure (BP) <140 mm Hg and diastolic BP <90 mm Hg or self-reported treatment for hypertension, was significantly higher in African Americans compared to whites (60% v 38%; P < .0001), whereas prevalence in Hispanic (42%) and Chinese participants (39%) did not differ significantly from that in whites. After adjustment for age, body mass index, prevalence of diabetes mellitus, and smoking, African American (odds ratio [OR] 2.21; 95% confidence interval [95% CI] 1.91-2.56) and Chinese (OR 1.30; 95% CI 1.07-1.56) ethnicity were significantly associated with hypertension compared to whites. Among hypertensive MESA participants, the percentage of treated but uncontrolled hypertension in whites (24%) was significantly lower than in African Americans (35%, P < .0001), Chinese (33%, P = .003), and Hispanics (32%, P = .0005), but only African-American race/ethnicity remained significantly associated with treated but uncontrolled hypertension after controlling for socioeconomic factors (OR 1.35; 95% CI 1.07-1.71). Diuretic use was lowest in the Chinese (22%) and Hispanic participants (32%) and was significantly lower in these groups compared with white participants (47%; P < .0001 for both comparisons). CONCLUSIONS: Programs to improve hypertension treatment and control should focus on a better understanding of differences in the prevalence of hypertension and hypertension control among minority groups in the United States, especially African Americans, compared with whites, and on techniques to prevent hypertension and improve control in high-risk groups.

Black or African American↗

Diversity and consistency: the challenge of maintaining quality in a multidisciplinary workforce.

Non-physician clinicians have become prominent providers of patient services within the practice of medicine. They include nurse practitioners and clinical nurse specialists, physician assistants, the alternative and complementary disciplines (chiropractic, naturopathy and acupuncture), mental health providers (psychologists, clinical social workers, counsellors and therapists) and specialty disciplines (optometrists, podiatrists, nurse anaesthetists and nurse-midwives). Although these various disciplines have differing histories and philosophic frameworks, which create distinctive approaches to patient care, they have shared a struggle to obtain recognition and autonomy through state licensure, to expand their state-granted practice prerogatives and to achieve broader reimbursement from third-party payers and managed care. Most entered into a growth spurt beginning in the early 1990s. All now provide care that not only overlaps that of physicians but that complements and supplements that care. The central question is, how does their care contribute to quality? The evidence thus far shows that non-physician clinicians throughout the range of disciplines can produce high-quality outcomes under particular circumstances. However, the strongest body of evidence is derived from care that is at the least complex end of the clinical spectrum or that is provided under the umbrella of physicians. Unfortunately, few studies have critically examined the outcomes of non-physician clinicians at the leading edge of their practice prerogatives and under conditions that are free of physician oversight. Thus, while the principle that they can deliver high quality care within the practice of medicine is unequivocally true, more research is needed to test this principle under conditions of greater clinical complexity and autonomy, and, pending the results of such research, caution must be exercised in applying this principle too broadly.

Humans↗

Associations between hypertension and genes in the renin-angiotensin system.

The genes of the renin-angiotensin system have been subjected to intense molecular scrutiny in cardiovascular disease studies, but their contribution to risk is still uncertain. In this study, we sampled 192 African American and 153 European American families (602 and 608 individuals, respectively) to evaluate the contribution of variations in genes that encode renin-angiotensin system components of susceptibility to hypertension. We genotyped 25 single-nucleotide polymorphisms in the renin-angiotensin system genes ACE, AGT, AGTR1, and REN. The family-based transmission/disequilibrium test was performed with each single-nucleotide polymorphism and with the multilocus haplotypes. Two individual single-nucleotide polymorphisms were significantly associated with hypertension among African Americans, and this result persisted when both groups were combined. The associations were confirmed in haplotype analysis for REN, AGTR1, and ACE in African Americans. Consistent but less significant evidence was found in European Americans. We also randomly sampled unrelated individuals across families to obtain 84 cases and 108 controls among the African Americans and 41 cases and 113 controls in the European Americans. Single-nucleotide polymorphism and haplotype analyses again showed consistent, albeit weaker, results. Thus, in this biracial population sample, we find evidence that interindividual variation in the renin-angiotensin system genes contributes to hypertension risk.

Adult↗

A genome-wide scan for body mass index among Nigerian families.

OBJECTIVE: Interest in mapping genetic variants that are associated with obesity remains high because of the increasing prevalence of obesity and its complications worldwide. Data on genetic determinants of obesity in African populations are rare. RESEARCH METHODS AND PROCEDURES: We have undertaken a genome-wide scan for body mass index (BMI) in 182 Nigerian families that included 769 individuals. RESULTS: The prevalence of obesity was only 5%, yet polygenic heritability for BMI was in the expected range (0.46 +/- 0.07). Tandem repeat markers (402) were typed across the genome with an average map density of 9 cM. Pedigree-based analysis using a variance components linkage model demonstrated evidence for linkage on chromosome 7 (near marker D7S817 at 7p14) with a logarithm of odds (LOD) score of 3.8 and on chromosome 11 (marker D11S2000 at 11q22) with an LOD score of 3.3. Weaker evidence for linkage was found on chromosomes 1 (1q21, LOD = 2.2) and 8 (8p22, LOD = 2.3). Several candidate genes, including neuropeptide Y, DRD2, APOA4, lamin A/C, and lipoprotein lipase, lie in or close to the chromosomal regions where strong linkage signals were found. DISCUSSION: The findings of this study suggest that, as in other populations with higher prevalences of obesity, positive linkage signals can be found on genome scans for obesity-related traits. Follow-up studies may be warranted to investigate these linkages, especially the one on chromosome 11, which has been reported in a population at the opposite end of the BMI distribution.

Adult↗

Income, education, and blood pressure in adults in Jamaica, a middle-income developing country.

BACKGROUND: At present, little is known about how socioeconomic status (SES) is related to blood pressure (BP) and hypertension in developing countries. This cross-sectional study examined associations between SES and BP in 2082 adults from a peri-urban area of Jamaica, a middle-income developing country. METHODS: Hypertension (systolic BP >/=140 mmHg, diastolic BP >/=90 mmHg or current hypertensive medication use) was estimated based on self-reported medication use and the mean of the second and third of three manual BP measurements. Income and education were self-reported. Linear or logistic regressions were used to estimate multivariate associations between BP or hypertension and SES. RESULTS: Hypertension prevalence was 20% in men and 28% in women. In both men and women, the income distributions of BP and hypertension were non-linear, indicating elevated levels in low as well as in high-income groups. In contrast to the negative relationships typical for industrialized countries, multivariate-adjusted BP and hypertension were highest in the wealthiest women. In men with some high school education, income was positively associated with BP, while there were negative associations in men with lesser education. Unlike women, mean BP were highest in poor men with limited education. Low SES men were also least likely to receive diagnosis and treatment. CONCLUSIONS: Socioeconomic status is related to BP and hypertension in Jamaica, although relationships are non-linear. Behavioural and environmental factors that explain elevated BP among both low and high SES adults in developing countries must be identified to develop effective prevention strategies.

Adult↗

Linkage for BMI at 3q27 region confirmed in an African-American population.

Significant and suggestive linkage for BMI on 3q27 has been reported by several groups, including our own study in African Americans. To further establish the linkage evidence on 3q27, we recruited an independent African-American sample comprising 545 individuals in 128 families. We genotyped 15 short tandem-repeat markers evenly spaced in the 112 cM region around the peak on 3q27 identified in our earlier study. Multipoint linkage analysis by GENEHUNTER2 gave the maximum logarithm of odds (LOD) score 2.4 at map position 188 cM in this sample. When we combined the two samples, linkage evidence was increased to a maximum LOD score (MLS) of 4.3 (point-wise P = 4.34 x 10(-6)) at 188 cM, with a 7 cM 1-LOD-drop interval around the peak. The multiple replications of linkage evidence in the region on 3q27 strongly confirm its potential importance as a candidate region in the search for obesity-related genes.

Adult↗

Angiotensin-1-converting enzyme (ACE) plasma concentration is influenced by multiple ACE-linked quantitative trait nucleotides.

Circulating angiotensin-1-converting enzyme (ACE) is a highly heritable trait, and a major component of the genetic variance maps to the region of the ACE gene. The strong effect of the locus, and the interest in ACE as a candidate gene for cardiovascular disorders, has led to extensive investigation of its relationship to the ACE phenotype, providing one of the most complete examples of quantitative trait locus (QTL) analysis in humans. Resequencing of ACE followed by haplotype analysis in families of British and French origin has shown that the genetic variants that are primarily associated with the ACE trait map to an 18 kb interval flanked by two intragenic, ancestral recombination breakpoints. This critical interval contains dozens of ACE-associated variants in Caucasians, but identification of which of these directly influence ACE concentration is ambiguous because of the almost complete linkage disequilibrium in European populations. In a complementary sequencing and genotyping study of individuals from West African families, we show that this population has much greater haplotype diversity across the gene. Through analysis of the contrasting relationships of the trait phenotype with haplotypes that carry different allelic combinations from those observed in Caucasians, we demonstrate that (at least) two major intragenic sites within the critical interval and (at least) one minor promoter site are associated with the ACE quantitative trait through additive effects. These results point to the importance of analysing diverse populations with different gene genealogies in gene-association studies.

Black People↗

Detecting recent positive selection in the human genome from haplotype structure.

The ability to detect recent natural selection in the human population would have profound implications for the study of human history and for medicine. Here, we introduce a framework for detecting the genetic imprint of recent positive selection by analysing long-range haplotypes in human populations. We first identify haplotypes at a locus of interest (core haplotypes). We then assess the age of each core haplotype by the decay of its association to alleles at various distances from the locus, as measured by extended haplotype homozygosity (EHH). Core haplotypes that have unusually high EHH and a high population frequency indicate the presence of a mutation that rose to prominence in the human gene pool faster than expected under neutral evolution. We applied this approach to investigate selection at two genes carrying common variants implicated in resistance to malaria: G6PD and CD40 ligand. At both loci, the core haplotypes carrying the proposed protective mutation stand out and show significant evidence of selection. More generally, the method could be used to scan the entire genome for evidence of recent positive selection.

Africa↗