Department of Medical Biochemistry
Permanent URI for this collectionhttp://197.255.125.131:4000/handle/123456789/23049
Browse
15 results
Search Results
Item Low HDL-cholesterol with normal triglyceride levels is the most common lipid pattern in West Africans and African Americans with metabolic syndrome: Implications for cardiovascular disease prevention(CVD Prevention and Control, 2010-09) Sumner, A.E.; Zhou, J.; Doumatey, A.; Imoisili, O.E.; Amoah, A.; Acheampong, J.; Oli, J.; Johnson, T.; Adebamowo, C.; Rotimi, C.N.Background: Although designed to predict cardiovascular disease and type 2 diabetes mellitus, the Metabolic Syndrome (MetSyn) under-predicts these conditions in African Americans (AA). Failure of MetSyn in AA is often attributed to their relative absence of hypertriglyceridemia. It is unknown if the African experience with MetSyn will be similar or different to that in AA. Focusing on the lipid profile, our goal was to determine in West Africans (WA) and AA the pattern of variables that leads to the diagnosis of the MetSyn. Methods: Cross-sectional analysis of 1296 subjects (364 WA, 44% male, 932 AA, 46% male). WA were from urban centers in Nigeria and Ghana and enrolled in the Africa America Diabetes Mellitus Study. AA lived in Washington, DC and participated in the Howard University Family Study. Results: The prevalence of MetSyn was different in WA women and men: 42% vs.19%, P < 0.001, and in AA women and men: 25% vs.17%, P < 0.01. The three variables that most often led to the diagnosis of MetSyn in WA and AA were: low HDL-C, central obesity and hypertension. Less than 40% of AA and less than 25% of WA with the MetSyn had hypertriglyceridemia. Conclusions: Elevated triglyceride levels were uncommon in both WA and AA with MetSyn. As the relative absence of hypertriglyceridemia is associated with a lack of efficacy of MetSyn in AA, caution is warranted in diagnosing MetSyn in WA, the ancestral population of AA. Prospective studies are necessary to determine if an ethnic-specific reformulation of the MetSyn scoring system for lipids might optimize risk identification in black populations.Item In search of susceptibility genes for type 2 diabetes in west africa: The design and results of the first phase of the AADM study(Annals of Epidemiology, 2001) Rotimi, C.N.; Dunston, G.M.; Berg, K.; Akinsete, O.; Amoah, A.; Owusu, S.; Acheampong, J.; Boateng, K.; Oli, J.; Okafor, G.; Onyenekwe, B.; Osotimehin, B.; Abbiyesuku, F.; Johnson, T.; Fasanmade, O.; Furbert-Harris, P.; Kittles, R.; Vekich, M.; Adegoke, O.; Bonney, G.; Collins, F.PURPOSE: The purpose of this study is to map type 2 diabetes susceptibility genes in West African ancestral populations of African-Americans, through an international collaboration between West African and US investigators. DESIGN AND METHODS: Affected sib-pairs (ASP) along with unaffected spouse controls are being enrolled and examined in West Africa, with two sites established in Ghana (Accra and Kumasi) and three in Nigeria (Enugu, Ibadan, and Lagos). Eligible participants are invited to study clinics to obtain detailed epidemiologic, family, and medical history information. Blood samples are drawn from each participant to measure glucose, insulin, C-peptide, total cholesterol, LDL, HDL, triglycerides, albumin, creatinine, urea, uric acid, total calcium and to detect autoantibodies to glutamic acid decarboxylase (GAD). DNA is isolated from frozen white blood cells obtained from 20 ml of EDTA whole blood samples. RESULTS: With full informed consent, 162 individuals from 78 families have been enrolled and examined since the Africa America Diabetes Mellitus (AADM) study began in June of 1997. Logistics of field examinations and specimen shipping have been successfully established. At the end of the third year of field activity (September 2000) the AADM study will have enrolled and performed comprehensive examination on 400 ASP with type 2 diabetes, for a minimum of 800 cases and 200 controls from Ghana and Nigeria. At the current participation rate, the goal of 400 sib-pairs and 200 controls will be met before the scheduled closing date. CONCLUSIONS: The AADM study will create a comprehensive epidemiologic and genetic resource that will facilitate a powerful genome-wide search for West African susceptibility genes to type 2 diabetes.Item Prevalence and determinants of diabetic retinopathy and cataracts in west african type 2 diabetes patients(Ethnicity and Disease, 2003-06) Rotimi, C.; Daniel, H.; Zhou, J.; Obisesan, A.; Chen, G.; Chen, Y.; Amoah, A.; Opoku, V.; Acheampong, J.; Agyenim-Boateng, K.; Eghan Jr., B.A.; Oli, J.; Okafor, G.; Ofeogbu, E.; Osotimehin, B.; Abbiyesuku, F.; Johnson, T.; Fasanmade, O.; Doumatey, A.; Aje, T.; Collins, F.; Dunston, G.Objective: To quantify the prevalence of, and risk factors for, diabetic retinopathy and cataracts in patients with type 2 diabetes, and their spouse controls, enrolled from 5 centers in 2 West African countries (Ghana and Nigeria). Method: The analysis cohort was made up of 840 subjects with type 2 diabetes, and their 191 unaffected spouse controls, who were enrolled and examined in Lagos, Enugu, and Ibadan, in Nigeria, and in Accra and Kumasi, in Ghana. A diagnosis of diabetic retinopathy was made only where a participant had a minimum of one microaneurysm in any field, as well as exhibiting hemorrhages (dot, blot, or flame shaped), and maculopathy (with or without clinically significant edema). Results: Average duration of diabetes was 7.0 years, and mean age at diagnosis was 46.5 years. Prevalence of diabetic retinopathy was 17.9%. Cataracts were present in 44.9% of the patients with type 2 diabetes, and in 18.3% of spouse controls. The risk of developing retinopathy increased more than 3-fold for patients at the highest fasting plasma glucose (FPG) level (OR=3.4; 95% CI, 1.8-6.3), compared to patients at the lowest FPG level. The odds ratios for persons with diabetes for 10 years or more, compared to persons with diabetes for less than 5 years, was 7.3 (95% CI, 4.3-12.3) for retinopathy, and 2.6 (95% CI, 1.5-4.5) for cataracts. Conclusions: Cataracts were a more important cause of vision impairment than was diabetic retinopathy in this cohort. The prevalence of cataracts in patients with diabetes was more than twice that of their spouse controls, indicating that type 2 diabetes is an important risk factor for cataract formation. Individuals who developed type 2 diabetes at an earlier age were more likely to develop both diabetic retinopathy and cataracts. A strong positive association was observed between FPG level, duration of diabetes, and risk of retinopathy and cataracts. The low prevalence of retinopathy and cataracts observed within the first 5 years of diagnosis of diabetes in this cohort, suggests that intensive blood glucose control may reduce the risk of the development and progression of retinopathy and cataracts. In this regard, early eye examination, preferably at first presentation of elevated blood glucose, is highly recommended.Item The drakensberg declaration on the control of rheumatic fever and rheumatic heart disease in africa(South African Medical Journal, 2006-03) Mayosi, B.; Robertson, K.; Volmink, J.; Adebo, W.; Akinyore, K.; Amoah, A.; Bannerman, C.; Biesman-Simons, S.; Carpetis, J.; Cilliers, A.; Commerford, P.; Croasdale, A.; Damasceno, A.; Dean, J.; Dean, M.; De-Souza, R.; Filipe, A.; Hugo-Hamman, C.; Jurgens-Clur, S.A.; Kombila-Koumba, P.; Kotzenberg, C.; Lawrenson, J.; Manga, P.; Matenga, J.; Mathivha, T.; Mntla, P.; Mocumbi, A.; Mokone, T.; Ogola, E.; Omokhodion, S.; Palweni, C.; Pearce, A.; Salo, A.; Thomas, B.; Walker, K.; Wiysonge, C.; Zaher, S.Item Circulating adiponectin is associated with renal function independent of age and serum lipids in West Africans(International Journal of Nephrology, 2012) Doumatey, A.P.; Zhou, J.; Huang, H.; Adeleye, J.; Balogun, W.; Fasanmade, O.; Johnson, T.; Oli, J.; Okafor, G.; Amoah, A.; Eghan, B.; Agyenim-Boateng, K.; Acheampong, J.; Adebamowo, C.; Adeyemo, A.; Rotimi, C.N.Adiponectin, a protein secreted by adipose tissue, has been associated with renal dysfunction. However, these observations have not been adequately investigated in large epidemiological studies of healthy individuals in general and in African populations in particular. Hence, we designed this study to evaluate the relationship between adiponectin and renal function in a large group of nondiabetic West Africans. Total adiponectin was measured in 792 participants. MDRD and Cockroft-Gault (CG-) estimated GFR were used as indices of renal function. Linear and logistic regression models were used to determine the relationship between adiponectin and renal function. Adiponectin showed an inverse relationship with eGFR in univariate (Beta MDRD = - 0.18, Beta CG = - 0.26) and multivariate (Beta MDRD = - 0.10, Beta CG = - 0.09) regression analyses. The multivariate models that included age, sex, BMI, hypertension, smoking, HDL-C, LDL-C, triglycerides, and adiponectin explained 30 and 55.6 of the variance in GFR estimated by MDRD and CG methods, respectively. Adiponectin was also a strong predictor of moderate chronic kidney disease (defined as eGFR 60 mL/min/1.73 m 2). We demonstrate that adiponectin is associated with renal function in nondiabetic West Africans. The observed relationship is independent of age and serum lipids. Our findings suggest that adiponectin may have clinical utility as a biomarker of renal function.Item Relationships among obesity, inflammation, and insulin resistance in african americans and west africans(Obesity, 2010-03) Doumatey, A.P.; Lashley, K.S.; Huang, H.; Zhou, J.; Chen, G.; Amoah, A.; Agyenim-Boateng, K.; Oli, J.; Fasanmade, O.; Adebamowo, C.A.; Adeyemo, A.A.; Rotimi, C.N.Several research studies in different populations indicate that inflammation may be the link between obesity and insulin resistance (IR). However, this relationship has not been adequately explored among African Americans, an ethnic group with disproportionately high rates of obesity and IR. In this study, we conducted a comparative study of the relationship among adiposity, inflammation, and IR in African Americans and West Africans, the ancestral source population for African Americans. The associations between obesity markers (BMI and waist-to-hip ratio (WHR)), inflammatory markers (high-sensitivity C-reactive protein (hsCRP), haptoglobin, interleukin (IL)-6, and tumor necrosis factor (TNF)-α), and IR (homeostasis model assessment of insulin resistance (HOMA IR)) were evaluated in 247 West Africans and 315 African Americans. In average, African Americans were heavier than the West Africans (by an average of 1.6 BMI units for women and 3 BMI units for men). Plasma hsCRP, haptoglobin, and IL-6 (but not TNF-α level) were higher in African Americans than in West Africans. In both populations, BMI was associated with markers of inflammation and with HOMA IR, and these associations remained significant after adjusting for sex and age. However, the pattern of associations between measured inflammatory markers and IR was different between the two groups. In West Africans, hsCRP was the only inflammatory marker associated with IR. In contrast, hsCRP, haptoglobin, and IL-6 were all associated with IR in African Americans. Interestingly, none of the associations between markers of inflammation and IR remained significant after adjusting for BMI. This finding suggests that in African Americans, the relationship between inflammatory markers and IR is mediated by adiposity.Item C-reactive protein (CRP) promoter polymorphisms influence circulating CRP levels in a genome-wide association study of African Americans(Human Molecular Genetics, 2012-07) Doumatey, A.P.; Chen, G.; Ayele, F.T.; Zhou, J.; Erdos, M.; Shriner, D.; Huang, H.; Adeleye, J.; Balogun, W.; Fasanmade, O.; Johnson, T.; Oli, J.; Okafor, G.; Amoah, A.; Eghan, B.A.; Agyenim-Boateng, K.; Acheampong, J.; Adebamowo, C.; Gerry, N.P.; Christman, M.F.; Adeyemo, A.; Rotimi, C.N.C-reactive protein (CRP) is an acute phase reactant protein produced primarily by the liver. Circulating CRP levels are influenced by genetic and non-genetic factors, including infection and obesity. Genome-wide association studies (GWAS) provide an unbiased approach towards identifying loci influencing CRP levels. None of the six GWAS for CRP levels has been conducted in an African ancestry population. The present study aims to: (i) identify genetic variants that influence serum CRP in African Americans (AA) using a genome-wide association approach and replicate these findings in West Africans (WA), (ii) assess transferability of major signals for CRP reported in European ancestry populations (EA) to AA and (iii) use the weak linkage disequilibrium (LD) structure characteristic of African ancestry populations to fine-map the previously reported CRP locus. The discovery cohort comprised 837 unrelated AA, with the replication of significant single-nucleotide polymorphisms (SNPs) assessed in 486 WA. The association analysis was conducted with 2 366 856 genotyped and imputed SNPs under an additive genetic model with adjustment for appropriate covariates. Genome-wide and replication significances were set at P < 5 × 10-8 and P < 0.05, respectively. Ten SNPs in (CRP pseudogene-1) CRPP1 and CRP genes were associated with serum CRP (P = 2.4 × 10-09 to 4.3 × 10-11). All but one of the top-scoring SNPs associated with CRP in AA were successfully replicated in WA. CRP signals previously identified in EA samples were transferable to AAs, and we were able to fine-map this signal, reducing the region of interest from the 25 kb of LD around the locus in the HapMap CEU sample to only 8 kb in our AA sample.Item Calpain-10 gene polymorphisms and type 2 diabetes in West Africans: The Africa America Diabetes Mellitus (AADM) Study(Annals of Epidemiology, 2005-02) Chen, Y.; Kittles, R.; Zhou, J.; Chen, G.; Adeyemo, A.; Panguluri, R.K.; Chen, W.; Amoah, A.; Opoku, V.; Acheampong, J.; Agyenim-Boateng, K.; Eghan Jr., B.A.; Nyantaki, A.; Oli, J.; Okafor, G.; Ofeogbu, E.; Osotimehin, B.; Abbiyesuku, F.; Johnson, T.; Fasanmade, O.; Rufus, T.; Furbert-Harris, P.; Daniel, H.I.; Berg, K.A.; Collins, F.S.; Dunston, G.M.; Rotimi, C.N.To investigate whether the three single nucleotide polymorphisms (SNPs), SNP-43, -56, and -63 of CAPN10 were associated with type 2 diabetes in a West African cohort. A total of 347 diabetic subjects and 148 unaffected controls from four ethnic groups in two West African countries were enrolled in this study. After genotyping three SNPs of CAPN10 and one SNP from CYP19, the allele, genotype, and haplotype frequencies as well as the odds ratios were calculated to test their association with type 2 diabetes. None of the alleles or genotypes was associated with type 2 diabetes. Although statistical analysis indicated that haplotype 221 was associated with type 2 diabetes (OR, 3.765; 95% CI, 1.577-8.989) in the two ethnic groups of Nigeria, the same haplotype did not show any association with type 2 diabetes in the two ethnic groups in Ghana (OR, 0.906; 95% CI, 0.322-2.552). Considering the relatively low frequency of haplotype 221 and that none of the haplotypes including 221 was associated with any of the diabetes-related quantitative traits tested, it is concluded that SNP-43, -56, and -63 of the CAPN10 gene variants may play a limited role in the risk of type 2 diabetes risks in this cohort of West Africans.Item A genome-wide search for linkage to renal function phenotypes in West Africans with type 2 diabetes(American Journal of Kidney Diseases, 2007-03) Chen, G.; Adeyemo, A.A.; Zhou, J.; Chen, Y.; Doumatey, A.; Lashley, K.; Huang, H.; Amoah, A.; Agyenim-Boateng, K.; Eghan Jr., B.A.; Okafor, G.; Acheampong, J.; Oli, J.; Fasanmade, O.; Johnson, T.; Rotimi, C.Background: Reduced renal function often is a major consequence of diabetes and hypertension. Although several indices of renal function (eg, creatinine clearance) are clearly heritable and show linkage to several genomic regions, the specific underlying genetic determinants are still being sought. The purpose of this study is to conduct a genome-wide search for regions linked to 3 renal function phenotypes, serum creatinine, creatinine clearance, and glomerular filtration rate (GFR), in persons with type 2 diabetes. Methods: A genome-wide panel of 372 autosomal short tandem repeat markers at an average spacing of 9 centimorgan were typed in 691 patients with type 2 diabetes (321 sib pairs and 36 half-sib pairs) in an affected sib pair study in West Africa. Linkage analysis was conducted with the 3 phenotypes by using a multipoint variance components linkage method. Results: Creatinine clearance showed higher logarithm of odds (LOD) score than the other 2 phenotypes. Linkage to creatinine clearance was observed on chromosomes 16 (marker D16S539, LOD score of 3.56, empirical P = 0.0001), 17 (D17S1298, LOD score of 2.08, empirical P = 0.0018), and 7 (D7S1818, LOD score of 1.84, nominal P = 0.00181, empirical P = 0.0022). Maximum LOD scores for serum creatinine were observed on chromosomes 10 (D10S1432, LOD score of 2.53, empirical P = 0.0001) and 3 (D3S2418, LOD score of 2.21, empirical P = 0.0003) and for GFR on chromosomes 6 (D6S1040, LOD score of 2.08, empirical P = 0.0001) and 8 (D8S256, LOD score of 1.80, empirical P = 0.0001). Several of these results are replications of significant findings from other genome scans. Conclusion: A genome-wide scan for serum creatinine, creatinine clearance, and GFR in a West African sample showed linkage regions that may harbor genes influencing variation in these phenotypes. Potential candidate genes in these regions that have been implicated in diabetic nephropathy and/or renal damage in models of hypertension include CYBA (or P22PHOX) (16q24), NOX1 (10q22), and NOX3 (6q25.1-q26)Item A genome-wide scan for quantitative trait loci linked to obesity phenotypes among West Africans(International Journal of Obesity, 2005-03) Chen, G.; Adeyemo, A.A.; Johnson, T.; Zhou, J.; Amoah, A.; Owusu, S.; Acheampong, J.; Agyenim-Boateng, K.; Eghan Jr., B.A.; Oli, J.; Okafor, G.; Abbiyesuku, F.; Dunston, G.M.; Chen, Y.; Collins, F.; Rotimi, C.OBJECTIVE: To identify quantitative trait loci (QTL) for three obesity phenotypes: body mass index (BMI), fat mass (FM) and percent body fat (PBF) in West Africans with type 2 diabetes (T2DM). DESIGN: An affected sibling pair (ASP) design, in which both siblings had T2DM. Obesity was analyzed as a quantitative trait using a variance components approach. SUBJECTS: Sib-pairs affected with T2DM from the Africa America Diabetes Mellitus (AADM) study, comprising 321 sibling pairs and 36 half-sibling pairs. MEASUREMENTS: Weight was measured on an electronic scale to the nearest 0.1 kg, and height was measured with a stadiometer to the nearest 0.1 cm. Body composition was estimated using bioelectric impedance analysis (BIA). Genotyping was carried out at the Center for Inherited Disease Research (CIDR) with a panel of 390 trinucleotide and tetranucleotide repeats. RESULTS: The obesity-related phenotype showing the strongest linkage evidence was PBF on chromosome 2 (LOD 3.30 at 72.6 cM, marker D2S739). Suggestive linkage to FM was found on chromosomes 2 (LOD 2.56 at 80.4 cM) and 5 (LOD 2.25 at 98 cM, marker D5S1725). The highest LOD score for BMI was 1.68 (chromosome 4, 113.8 cM). The areas of linkage for the three phenotypes showed some clustering as all three phenotypes were linked to the same regions of 2p13 and 5q14, and our study replicated linkage evidence for several regions previously reported in other studies. CONCLUSION: We obtained evidence for several QTLs on chromosome 2, 4 and 5 to three obesity phenotypes. This study provides data on the genetics of obesity in populations that are currently under represented in the global effort directed at understanding the pathophysiology of excess adiposity in free living individuals.