Department of Medicine

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Browsing Department of Medicine by Author "Acheampong, J"

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    Open Access
    A genome wide quantitative trait linkage analysis for serum lipids in type 2 diabetes in an African population
    (Elsevier, 2005) Adeyemo, A.A; Johnson, T; Acheampong, J; Oli, J; Okafor, G; Amoah, A; Owusu, S; Agyenim-Boateng, K; Eghan, B.A Jr; Abbiyesuku, F; Fasanmade, O; Rufus, T; Doumatey, A; Chen, G; Zhou, J; Chen, Y; Fubert-Harris, P; Dunston, G; Collins, F; Rotimi, C
    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 9 cM. 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.
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    Open Access
    Genome-wide analysis identifies an african-specific variant in SEMA4D associated with body mass index
    (Wiley, 2017-04) Rotimi, C.N; Johnson, T; Chen, G; Adeyemo, A; Fasanmade, O; Shriner, D; Acheampong, J; Oli, J; Doumatey, A.P; Okafor, G; Bentley, A.R
    OBJECTIVE: The prevalence of obesity varies between ethnic groups. No genome-wide association study (GWAS) for body mass index (BMI) has been conducted in continental Africans. METHODS: We performed a GWAS for BMI in 1,570 West Africans (WA). Replication was conducted in independent samples of WA (n = 1,411) and African Americans (AA) (n = 9,020). RESULTS: We identified a novel genome-wide significant African-specific locus for BMI (SEMA4D, rs80068415; minor allele frequency = 0.008, P = 2.10 × 10-8 ). This finding was replicated in independent samples of WA (P = 0.013) and AA (P = 0.017). Individuals with obesity had higher serum SEMA4D levels compared to those without obesity (P < 0.0001), and elevated levels of serum SEMA4D were associated with increased obesity risk (OR = 4.2, P < 1 × 10-4 ). The prevalence of obesity was higher in individuals with the CT versus TT genotypes (55.6% vs. 22.9%). CONCLUSIONS: A novel variant in SEMA4D was significantly associated with BMI. Carriers of the C allele were 4.6 BMI units heavier than carriers of the T allele (P = 0.0007). This variant is monomorphic in Europeans and Asians, highlighting the importance of studying diverse populations. While there is evidence for the involvement of SEMA4D in inflammatory processes, this study is the first to implicate SEMA4D in obesity pathophysiology.
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    Open Access
    Genome-wide association study identifies African-ancestry specific variants for metabolic syndrome
    (2015-12) Tekola-Ayele, F; Doumatey, A.P; Shriner, D; Bentley, A.R; Chen, G; Zhou, J; Fasanmade, O; Johnson, T; Oli, J; Okafor, G; Eghan, B.A Jr; Agyenim-Boateng, K; Adebamowo, C; Amoah, A; Acheampong, J; Rotimi, C.N; Adeyemo, A
    The metabolic syndrome (MetS) is a constellation of metabolic disorders that increase the risk of developing several diseases including type 2 diabetes and cardiovascular diseases. Although genome-wide association studies (GWAS) have successfully identified variants associated with individual traits comprising MetS, the genetic basis and pathophysiological mechanisms underlying the clustering of these traits remain unclear. We conducted GWAS of MetS in 1,427 Africans from Ghana and Nigeria followed by replication testing and meta-analysis in another continental African sample from Kenya. Further replication testing was performed in an African American sample from the Atherosclerosis Risk in Communities (ARIC) study. We found two African-ancestry specific variants that were significantly associated with MetS: SNP rs73989312[A] near CA10 that conferred increased risk (P=3.86x10−8, OR=6.80) and SNP rs77244975[C] in CTNNA3 that conferred protection against MetS (P=1.63x10−8, OR=0.15). Given the exclusive expression of CA10 in the brain, our CA10 finding strengthens previously reported link between brain function and MetS. We also identified two variants that are not African specific: rs76822696[A] near RALYL associated with increased MetS risk (P=7.37x10−9, OR=1.59) and rs7964157[T] near KSR2 associated with reduced MetS risk (P=4.52x10−8, Pmeta=7.82x10−9, OR=0.53). The KSR2 locus displayed pleiotropic associations with triglyceride and measures of blood pressure. Rare KSR2 mutations have been reported to be associated with early onset obesity and insulin resistance. Finally, we replicated the LPL and CETP loci previously found to be associated with MetS in Europeans. These findings provide novel insights into the genetics of MetS in Africans and demonstrate the utility of conducting trans-ethnic disease gene mapping studies for testing the cosmopolitan significance of GWAS signals of cardio-metabolic traits.
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    Open Access
    A Genome-Wide Search for Linkage to Renal Function Phenotypes in West Africans With Type 2 Diabetes
    (W.B Saunders, 2007) Chen, G; Adeyemo, A.A; Zhou, J; Chen, Y; Doumatey, A; Lashley, K; Huang, H; Amoah, A; Agyenim-Boateng, K; Eghan, B.A Jr; 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 pheno- types. 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 pheno- types. 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).
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    Open Access
    Genome-wide search for susceptibility genes to type 2 diabetes in West Africans: Potential role of C-peptide
    (Elsevier, 2007-12) Chen, G; Adeyemo, A; Zhou, J; Chen, Y; Huang, H; Doumatey, A; Lashley, K; Agyenim-Boateng, K; Eghan, B.A Jr; Acheampong, J; Fasanmade, O; Johnson, T; Okafor, G; Oli, J; Amoah, A; Rotimi, C
    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.
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    Open Access
    Impact of Type 2 Diabetes on Impaired Kidney Function in Sub-Saharan African Populations
    (Frontiers Media, 2016-05) Adebamowo, S.N; Rotimi, C.N; Balogun, W; Fasanmade, O.A; Oli, J; Bentley, A.R; Adebamowo, C.A; Shriner, D; Johnson, T; Zhou, J; Chen, G; Okafor, G; Eghan, B Jr; Amoah, A.G; Acheampong, J; Agyenim-Boateng, K; Tekola-Ayele, F; Owusu, S; Adeleye, J
    BACKGROUND: Diabetes is a leading risk factor for impaired kidney function, an indicator of chronic kidney disease. The aim of this study was to examine the association between type 2 diabetes (T2D) and impaired kidney function among adults in sub-Saharan Africa (SSA). METHODS: Participants were enrolled from Ghana, Kenya, and Nigeria. Impaired kidney function was based on an estimated glomerular filtration rate <60 ml/min/1.73 m(2). Using logistic regression models, we conducted case-control analyses to estimate the multivariate-adjusted association of T2D and kidney function. RESULTS: We used data from 4815 participants for whom the mean (SD) age was 48 (15) years, 41% were male and 46% had T2D. Those with T2D were more likely to have impaired kidney function [13.4% (95% CI: 11.9-14.7)] compared to those without T2D [4.8% (95% CI: 4.0-5.6)], p-value <0.001. The multivariate odds ratio of impaired kidney function among those with type 2 diabetes was 1.50 (95% CI: 1.17-1.91) p-value = 0.001, compared to those without T2D. Also, individuals with T2D who were at least 60 years old, obese, hypertensive or dyslipidemic were more likely to have impaired kidney function compared to those without T2D. CONCLUSION: T2D was associated with 50% increased risk of impaired kidney function in this sample of adults from SSA. Interventions targeted at prevention, early diagnosis, and management of T2D are likely to reduce the burden of kidney disease in SSA.
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    Open Access
    Polymorphism of the endothelial nitric oxide synthase gene is associated with diabetic retinopathy in a cohort of West Africans
    (2007-04) Chen, Y; Huang, H; Zhou, J; Doumatey, A; Lashley, K; Chen, G; Agyenim-Boateng, K; Eghan, B.A; Acheampong, J; Fasanmade, O; Johnson, T; Akinsola, F.B; Okafor, G; Oli, J; Ezepue, F; Amoah, A; Akafo, S; Adeyemo, A; Rotimi, C.N
    Purpose: 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). Methods: We genotyped the deletion/insertion (4a/b) and the G894T polymorphisms of eNOS gene in a total of 575 persons. Results: 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. Conclusions: We observed a significant association between the 4a/b polymorphism of the eNOS and DR in our West African cohort.
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    Open Access
    Prevalence and determinants of diabetic retinopathy and cataracts in West African type 2 diabetes patients
    (2003) Rotimi, C; Daniel, H; Zhou, J; Obisesan, A; Chen, G; Chen, Y; Amoah, A; Opoku, V; Acheampong, J; Agyenim-Boateng, K; Eghan, B.A Jr; Oli, J; Okafor, G; Ofoegbu, 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 cata- racts 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 en- rolled and examined in Lagos, Enugu, and Iba- dan, in Nigeria, and in Accra and Kumasi, in Ghana. A diagnosis of diabetic retinopathy was made only where a participant had a mini- mum of one microaneurysm in any field, as well as exhibiting hemorrhages (dot, blot, or flame shaped), and maculopathy (with or with- out 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 reti- nopathy increased more than 3-fold for pa- tients at the highest fasting plasma glucose (FPG) level (OR􏰃3.4; 95% CI, 1.8–6.3), com- pared to patients at the lowest FPG level. The odds ratios for persons with diabetes for 10 years or more, compared to persons with di- abetes 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 impor- tant cause of vision impairment than was dia- betic retinopathy in this cohort. The preva- lence 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 as- sociation was observed between FPG level, duration of diabetes, and risk of retinopathy and cataracts. The low prevalence of retinop- athy 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