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Ayo P Doumatey,
Guanjie Chen,
Fasil Tekola Ayele,
Jie Zhou,
Michael Erdos,
Daniel Shriner,
Hanxia Huang,
Jokotade Adeleye,
Williams Balogun,
Olufemi Fasanmade, [......],
Godfrey Okafor,
Albert Amoah,
Benjamin A Eghan,
Kofi Agyenim-Boateng, Joseph Acheampong,
Clement Adebamowo,
Norman P Gerry,
Michael F Christman,
Adebowale Adeyemo,
Charles N Rotimi
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ABSTRACT: 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.
Human Molecular Genetics 04/2012; 21(13):3063-72. · 7.64 Impact Factor
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Amy Rebecca Bentley,
Ayo P Doumatey,
Guanjie Chen,
Hanxia Huang,
Jie Zhou,
Daniel Shriner,
Congqing Jiang,
Zhenjian Zhang,
Guozheng Liu,
Olufemi Fasanmade, [......],
Godfrey Okafor,
Benjamin A Eghan,
Kofi Agyenim-Boateng,
Jokotade Adeleye,
Williams Balogun,
Clement Adebamowo,
Albert Amoah, Joseph Acheampong,
Adebowale Adeyemo,
Charles N Rotimi
[show abstract]
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ABSTRACT: Low levels of high-density cholesterol (HDLc) accompany chronic kidney disease, but the association between HDLc and the estimated glomerular filtration rate (eGFR) in the general population is unclear. We investigated the HDLc-eGFR association in nondiabetic Han Chinese (HC, n = 1100), West Africans (WA, n = 1497), and African Americans (AA, n = 1539). There were significant differences by ancestry: HDLc was positively associated with eGFR in HC (β = 0.13, P < 0.0001), but negatively associated among African ancestry populations (WA: -0.19, P < 0.0001; AA: -0.09, P = 0.02). These differences were also seen in nationally-representative NHANES data (among European Americans: 0.09, P = 0.005; among African Americans -0.14, P = 0.03). To further explore the findings in African ancestry populations, we investigated the role of an African ancestry-specific nephropathy risk variant, rs73885319, in the gene encoding HDL-associated APOL1. Among AA, an inverse HDLc-eGFR association was observed only with the risk genotype (-0.38 versus 0.001; P = 0.03). This interaction was not seen in WA. In summary, counter to expectation, an inverse HDLc-eGFR association was observed among those of African ancestry. Given the APOL1 × HDLc interaction among AA, genetic factors may contribute to this paradoxical association. Notably, these findings suggest that the unexplained mechanism by which APOL1 affects kidney-disease risk may involve HDLc.
International journal of nephrology. 01/2012; 2012:748984.
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Fasil Tekola Ayele,
Ayo Doumatey,
Hanxia Huang,
Jie Zhou,
Bashira Charles,
Michael Erdos,
Jokotade Adeleye,
Williams Balogun,
Olufemi Fasanmade,
Thomas Johnson, [......],
Kofi Agyenim-Boateng, Joseph Acheampong,
Clement A Adebamowo,
Alan Herbert,
Norman Gerry,
Michael Christman,
Guanjie Chen,
Daniel Shriner,
Adebowale Adeyemo,
Charles N Rotimi
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ABSTRACT: Interleukins (ILs) are key mediators of the immune response and inflammatory process. Plasma levels of IL-10, IL-1Ra, and IL-6 are associated with metabolic conditions, show large inter-individual variations, and are under strong genetic control. Therefore, elucidation of the genetic variants that influence levels of these ILs provides useful insights into mechanisms of immune response and pathogenesis of diseases. We conducted a genome-wide association study (GWAS) of IL-10, IL-1Ra, and IL-6 levels in 707 non-diabetic African Americans using 5,396,780 imputed and directly genotyped single nucleotide polymorphisms (SNPs) with adjustment for gender, age, and body mass index. IL-10 levels showed genome-wide significant associations (p < 5 × 10(-8)) with eight SNPs, the most significant of which was rs5743185 in the PMS1 gene (p = 2.30 × 10(-10)). We tested replication of SNPs that showed genome-wide significance in 425 non-diabetic individuals from West Africa, and successfully replicated rs17365948 in the YWHAZ gene (p = 0.02). IL-1Ra levels showed suggestive associations with two SNPs in the ASB3 gene (p = 2.55 × 10(-7)), ten SNPs in the IL-1 gene family (IL1F5, IL1F8, IL1F10, and IL1Ra, p = 1.04 × 10(-6) to 1.75 × 10(-6)), and 23 SNPs near the IL1A gene (p = 1.22 × 10(-6) to 1.63 × 10(-6)). We also successfully replicated rs4251961 (p = 0.009); this SNP was reported to be associated with IL-1Ra levels in a candidate gene study of Europeans. IL-6 levels showed genome-wide significant association with one SNP (RP11-314E23.1; chr6:133397598; p = 8.63 × 10(-9)). To our knowledge, this is the first GWAS on IL-10, IL-1Ra, and IL-6 levels. Follow-up of these findings may provide valuable insight into the pathobiology of IL actions and dysregulations in inflammation and human diseases.
Immunogenetics 12/2011; 64(5):351-9. · 2.93 Impact Factor
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[show abstract]
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ABSTRACT: 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.
CVD Prev Control 09/2010; 5(3):75-80.
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Guanjie Chen,
Adebowale Adeyemo,
Jie Zhou,
Yuanxiu Chen,
Hanxia Huang,
Ayo Doumatey,
Kerrie Lashley,
Kofi Agyenim-Boateng,
Benjamin A Eghan, Joseph Acheampong,
Olufemi Fasanmade,
Thomas Johnson,
Godfrey Okafor,
Johnnie Oli,
Albert Amoah,
Charles Rotimi
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ABSTRACT: C-peptide is a substance that the pancreas releases into the circulation in equimolar amounts to insulin and has demonstrated important physiological effects which relate to the vascular field, in particular the microcirculation. For this analysis, we included 321 full and 36 half sibling pairs affected with type 2 diabetes (T2D) from West Africa. A genome-wide panel of 390 tri-nucleotide and tetra-nucleotide repeats with an average distance of 8.9 cM was performed on a total of 691 persons. Variance components based on multipoint linkage approach as implemented in SOLAR were performed for log C-peptide. Significant linkage evidences were observed on 10q23 at D10S2327 with a LOD score of 4.04 (nominal p-value=0.000008, empirical p-value=0.0004); and on 4p15 at D4S2632 with a LOD score of 3.48 (nominal p-value=0.000031, empirical p-value=0.0013). Other suggestive evidence of linkage were observed on 15q14 at D15S659 with a LOD score 2.41 (nominal p-value=0.000435, empirical p-value=0.0068), and on 18p11 near D18S976 with a LOD score 2.18 (nominal p-value=0.000771 and empirical p-value=0.0094). Interestingly, five positional candidate genes for diabetes and related complications are located in our linkage region (the pituitary adenylate cyclase activating polypeptide (PACAP in 18p11); the peroxisome proliferator-activated receptor gamma coactivator 1 (PPARGC1 in 4p15); PTEN, PPP1R5, and IDE located in 10q23. In conclusion, we identified four major genetic loci (10q23, 4p15, 15q14, and 18p11) influencing C-peptide concentration in West Africans with T2D.
Diabetes research and clinical practice 01/2008; 78(3):e1-6. · 2.16 Impact Factor
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Guanjie Chen,
Adebowale A Adeyemo,
Jie Zhou,
Yuanxiu Chen,
Ayo Doumatey,
Kerrie Lashley,
Hanxia Huang,
Albert Amoah,
Kofi Agyenim-Boateng,
Benjamin A Eghan,
Godfrey Okafor, Joseph Acheampong,
Johnnie Oli,
Olufemi Fasanmade,
Thomas Johnson,
Charles Rotimi
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ABSTRACT: 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.
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.
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.
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).
American Journal of Kidney Diseases 04/2007; 49(3):394-400. · 5.43 Impact Factor
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Yuanxiu Chen,
Hanxia Huang,
Jie Zhou,
Ayo Doumatey,
Kerrie Lashley,
Guanjie Chen,
Kofi Agyenim-Boateng,
Benjamin A Eghan, Joseph Acheampong,
Olufemi Fasanmade,
Thomas Johnson,
Folasade B Akinsola,
Godfrey Okafor,
Johnnie Oli,
Felix Ezepue,
Albert Amoah,
Stephen Akafo,
Adebowale Adeyemo,
Charles N Rotimi
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ABSTRACT: In addition to chronic hyperglycemia, there is increasing evidence that genetic factors may be important in the development of diabetes retinopathy (DR). Specifically, polymorphisms of the endothelial nitric oxide synthase gene (eNOS) have been reported to be associated with multiple health conditions including DR, hypertension, nephropathy, and cardiovascular diseases in several ethnic groups. However, there is a paucity of similar data in African Americans and other African populations. To address this issue, we investigated the potential association between polymorphisms of the eNOS gene and diabetes-related phenotypes in 384 persons with type 2 diabetes and 191 controls from two West African countries (Ghana and Nigeria).
We genotyped the deletion/insertion (4a/b) and the G894T polymorphisms of eNOS gene in a total of 575 persons.
The b/b genotype of the polymorphism was associated with a 2.4 fold increased risk of DR (95% CI 1.39-4.09). In contrast, we did not observe any association between the genotypes or alleles of G894T polymorphism with DR, hypertension, or nephropathy.
We observed a significant association between the 4a/b polymorphism of the eNOS and DR in our West African cohort.
Molecular vision 02/2007; 13:2142-7. · 2.20 Impact Factor
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Adebowale A Adeyemo,
Thomas Johnson, Joseph Acheampong,
Johnnie Oli,
Godfrey Okafor,
Albert Amoah,
Samuel Owusu,
Kofi Agyenim-Boateng,
Benjamin A Eghan,
Fayeofori Abbiyesuku,
Olufemi Fasanmade,
Theresa Rufus,
Ayo Doumatey,
Guanjie Chen,
Jie Zhou,
Yuanxiu Chen,
Paulette Furbert-Harris,
Georgia Dunston,
Francis Collins,
Charles Rotimi
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ABSTRACT: Lipid abnormalities are strongly linked with coronary heart disease and are common in type 2 diabetes. However, little is known about the genetic determinants of serum lipids in African populations. An autosomal genome scan was performed for linkage to five plasma lipid phenotypes (total cholesterol, triglycerides (TG), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C) and VLDL-cholesterol (VLDL-C)) in the Africa-America Diabetes Mellitus (AADM) study. Two hundred and ninety-five affected sibling pairs with type 2 diabetes mellitus enrolled from Ghana and Nigeria were genotyped for 390 microsatellite markers with an average inter-marker distance of 9cM. Multipoint variance components linkage analysis showed that HDL-C had a LOD score of 4.34 near marker D7S3061 and 3.00 near marker D7S513. Some clustering of linkage evidence to several lipid phenotypes was observed on chromosomes 5 (LDL-C, total cholesterol, VLDL-C), chromosome 7 (HDL-C, TG) and chromosome 19 (total cholesterol, LDL-C, TG). Principal component analysis of the five phenotypes yielded two factors, one (TG, HDL-C and VLDL) of which was linked to QTLs on chromosomes 2, 5 and 7, while the other (total cholesterol and LDL-C) was linked to a different set of QTLs on chromosomes 2, 5 and 18. Several of these regions have been reported to be linked to lipids in other studies. Follow up investigations are warranted in view of the central role serum lipids play in the aetiopathogenesis of cardiovascular disease.
Atherosclerosis 09/2005; 181(2):389-97. · 3.79 Impact Factor
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Yuanxiu Chen,
Rick Kittles,
Jie Zhou,
Guanjie Chen,
Adebowale Adeyemo,
Ramesh K Panguluri,
Weidong Chen,
Albert Amoah,
Victoria Opoku, Joseph Acheampong, [......],
Fayeofori Abbiyesuku,
Thomas Johnson,
Olufemi Fasanmade,
Theresa Rufus,
Paulette Furbert-Harris,
Harold I Daniel,
Kate A Berg,
Francis S Collins,
Georgia M Dunston,
Charles N Rotimi
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ABSTRACT: 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.
Annals of Epidemiology 03/2005; 15(2):153-9. · 3.21 Impact Factor
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Charles N Rotimi,
Guanjie Chen,
Adebowale A Adeyemo,
Paulette Furbert-Harris,
Debra Parish-Gause,
Jie Zhou,
Kate Berg,
Olufemi Adegoke,
Albert Amoah,
Samuel Owusu, [......],
Fayeofori Abbiyesuku,
Thomas Johnson,
Theresa Rufus,
Olufemi Fasanmade,
Rick Kittles,
Harold Daniel,
Yuanxiu Chen,
Georgia Dunston,
Francis S Collins,
Debra Guass
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ABSTRACT: The incidence of type 2 diabetes is growing rapidly, not only in developed countries but also worldwide. We chose to study type 2 diabetes in West Africa, where diabetes is less common than in the U.S., reasoning that in an environment where calories are less abundant, incident cases of type 2 diabetes might carry a proportionately greater genetic component. Through the Africa America Diabetes Mellitus (AADM) study, we carried out a genome-wide linkage analysis of type 2 diabetes in a cohort of 343 affected sibling pairs (691 individuals) enrolled from five West African centers in two countries (Ghana: Accra and Kumasi; Nigeria: Enugu, Ibadan, and Lagos). A total of 390 polymorphic markers were genotyped, and multipoint linkage analysis was conducted using the GENEHUNTER-PLUS and ASM programs. Suggestive evidence of linkage was observed in four regions on three chromosomes (12, 19, and 20). The two largest logarithm of odds scores of 2.63 and 1.92 for chromosomes 20q13.3 and 12q24, respectively, are particularly interesting because these regions have been reported to harbor diabetes susceptibility genes in several other populations and ethnic groups. Given the history of forced migration of West African populations during the slave trade, these results should have considerable relevance to the study of type 2 diabetes in African Americans.
Diabetes 04/2004; 53(3):838-41. · 8.29 Impact Factor
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Charles Rotimi,
Harold Daniel,
Jie Zhou,
Augustine Obisesan,
Guanjie Chen,
Yuanxiu Chen,
Albert Amoah,
Victoria Opoku, Joseph Acheampong,
Kofi Agyenim-Boateng, [......],
Godfrey Okafor,
Ester Ofoegbu,
Babatunde Osotimehin,
Fayeofori Abbiyesuku,
Thomas Johnson,
Olufemi Fasanmade,
Ayo Doumatey,
Temilolu Aje,
Francis Collins,
Georgia Dunston
[show abstract]
[hide abstract]
ABSTRACT: 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).
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).
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.
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.
Ethnicity & disease 02/2003; 13(2 Suppl 2):S110-7. · 0.90 Impact Factor
