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Biomedical subjects

A Luke

Publications and source records attributed to A Luke.

At least 19 recordsLinked to original sources
PubMed2006

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↗
PubMed2005

Meta-analysis of five genome-wide linkage studies for body mass index reveals significant evidence for linkage to chromosome 8p.

OBJECTIVE: To perform a meta-analysis of genome-wide linkage scans using body mass index (BMI) to identify genetic loci predisposing to obesity. DATA: A total of 13 published genome scans on obesity have used BMI as their primary end point. Five of these 13 groups agreed to provide detailed results from their scans that were required for a meta-analysis. Collectively, these five studies included a total of 2814 individuals from 505 families. METHODS: The results of the five studies were analysed using the GSMA (genome scans meta-analysis) method. RESULTS: The analysis revealed significant evidence for linkage of the quantitative phenotype BMI to 8p (P<0.0005).

Adult↗
PubMed2005

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↗
PubMed2005

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↗
PubMed2004

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↗
PubMed2004

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2000

Comparability of resting energy expenditure in Nigerians and U.S. blacks.

OBJECTIVE: To determine the influence of environmental factors on resting energy expenditure (REE) and its relationship to adiposity in two populations of West African origin, Nigerians and U.S. blacks. RESEARCH METHODS AND PROCEDURES: REE and body composition were measured in a cross-sectional sample of 89 Nigerian adults (39 women and 50 men), and 181 U.S. black adults (117 women and 65 men). Both groups represent randomly selected population samples. REE was measured by indirect calorimetry after an overnight fast in both sites using the same instrument. Body composition was estimated using bioelectrical impedance analysis (BIA) in 72 Nigerians and 156 U.S. participants. Multivariate regression analysis was used to determine the significant predictors of REE. The analyses were repeated in a set of 17 Nigerians and 28 U.S. blacks in whom body composition was measured using deuterium dilution. RESULTS: U.S. black adults were significantly heavier and had both more fat-free mass (FFM) and body fat than Nigerians. FFM was the only significant determinant of REE in both population groups, whether body composition was measured using BIA or deuterium dilution. The relationship between REE and body composition did not differ by site. There was no relationship between REE and adiposity. DISCUSSION: Differences in current environmental settings did not impact REE. The differences observed in mean levels of body fat between Nigerians and U.S. blacks were not the result of differences in REE adjusted for body composition.

Adipose Tissue↗
PubMed2000

Heritability of angiotensin-converting enzyme and angiotensinogen: A comparison of US blacks and Nigerians.

Angiotensinogen (AGT) and angiotensin I-converting enzyme (ACE) are heritable traits, but whether the environmental context influences heritability has not been examined. Known genetic factors explain only a portion of variation in AGT and ACE, and levels of both proteins are influenced by the environment. The African diaspora provides an opportunity to compare these traits in genetically related populations in contrasting environments. As part of a study of the genetics of hypertension, we examined families that included 1449 Nigerians and 1147 African Americans. Body mass index (weight [kg]/height [m](2)) was 21 kg/m(2) in Nigeria and 29 kg/m(2) in the United States, which is consistent with a large environmental contrast. AGT was considerably higher among African Americans (1919 versus 1396, P<0.01), whereas ACE was higher in Nigerians (630 versus 517, P<0.01). A household effect was observed among the Nigerian families (spouse correlations 0.30 for AGT, 0.18 for ACE), and correlations among first-degree relatives were large (0.42 to 0. 51 and 0.36 to 0.38 for AGT and ACE, respectively). Among African Americans, the familial aggregations of AGT and ACE were very limited, and the familial correlation for AGT was not different from zero. Heritability was 77% for AGT and 67% for ACE in Nigeria and 18% for AGT and ACE in the United States. The familial patterns of body mass index and blood pressure were similar among both family sets. In conclusion, less familial aggregation was observed for AGT and ACE in the United States than in Nigeria, most likely reflecting a greater random individual environmental effect on these traits. Variation in heritability of traits could influence the power of epidemiological studies to identify genetic effects.

Adult↗
PubMed1999

The long isoform uncoupling protein-3 (UCP3L) in human energy homeostasis.

The biological role(s) proposed for UCP3 in energy homeostasis have been based primarily upon amino acid sequence homology to UCP1. Spontaneous mutations of UCP3> have been described in humans, but not in rodents. The functional consequences-or lack thereof-of these mutations in humans will be of great importance in elucidating the biology of this protein. The results of two such studies are summarized here.

Animals↗
PubMed1999

Evidence of a major gene effect for angiotensinogen among Nigerians.

To dissect the genetic pathway of hypertension, we measured angiotensinogen in 685 members of 186 families recruited from a rural community in southwest Nigeria. Commingling and segregation analyses were carried out. A mixture of two and/or three distributions fits the data significantly better than a single distribution in commingling analysis, suggesting a major gene effect. Segregation analysis confirmed that a recessive major gene model for low values of angiotensinogen provides the best fit to the data and about 13% of the variance was due to the recessive gene segregation.

Adolescent↗
PubMed1999

Differential representations of memory T cell subsets are characteristic of polarized immunity in leprosy and atopic diseases.

We identified functionally polarized subsets of CD4 memory T cells on the basis of the expression of CD11a, CD45RA and CD62L. Within the several phenotypically distinct subsets of CD4 memory cells are two that, upon stimulation, produce primarily IL-4 (MT(2), CD45RA(-)CD62L(+)CD11a(dim)) or primarily IFN-gamma (MT(1), CD45RA(-)CD62L(-)CD11a(bright)). In addition, four other phenotypically distinct subsets of CD4 cells have unique cytokine profiles. To determine the clinical relevance of the representation of these cell types, we analyzed blood from patients with the chronic diseases leprosy and atopy. These diseases are characterized as immunologically polarized, since T cell responses in affected individuals are often strongly biased towards T(h)1 (dominated by IFN-gamma production) or T(h)2 (IL-4 production). We show here that this polarization reflects homeostatic or differentiation mechanisms affecting the representation of the functionally distinct subsets of memory CD4 T cells, MT(1) and MT(2). Significantly, the representation of the MT(1) and MT(2) subsets differs dramatically between subjects with tuberculoid leprosy (a T(h)1 disease), or lepromatous leprosy or atopic disease (T(h)2 diseases). However, there was no difference in the cytokine profiles of these or any of the other finely resolved CD4 subsets, when compared between individuals across all disease states. Thus, it is the representation of these subsets in peripheral blood that is diagnostic of the polarized state of the immune system.

CD4-Positive T-Lymphocytes↗