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The TCF7L2 rs7903146 (T) allele is associated with type 2 diabetes in urban Ghana: a hospital-based case-control study.

ABSTRACT: BACKGROUND: Type 2 diabetes mellitus is increasing dramatically in sub-Saharan Africa, and genetic predisposition is likely involved in that. Yet, genetic variants known to confer increased susceptibility among Caucasians are far from being established in African populations. In Ghanaian adults, we examined associations of several of these polymorphisms with type 2 diabetes. METHODS: A hospital-based case-control study on type 2 diabetes (and hypertension) was conducted in Kumasi, Ghana. TCF7L2 rs7903146, KCNJ11 rs5219, PPAR? rs1801282 and CAPN10 rs3842570, rs3792267, and rs5030952 were typed and associations with type 2 diabetes and phenotypic traits examined. RESULTS: 675 patients with type 2 diabetes and 377 controls were compared. The minor allele frequency of the TCF7L2 (T) allele was 0.33. In the multivariate model, this allele increased the risk of type 2 diabetes by 39% (95% confidence interval (CI), 1.07-1.81; p?=?0.014). The minor alleles KCNJ11 (G) and PPAR? (G) were practically absent (each, 0.001). Minor allele frequencies of CAPN10 were for -43 (A) 0.11 and for -63 (C) 0.46. These variants showed no significant associations with type 2 diabetes. Two CAPN10 haplotypes tended to protect against type 2 diabetes: 211 (aOR, 0.32; 95% CI, 0.03-1.92; p?=?0.31) and 221 (aOR, 0.73; 95% CI, 0.48-1.10; p?=?0.13). CONCLUSIONS: In urban Ghana, the frequency of the TCF7L2 rs7903146 (T) allele is comparable to the one in Caucasians; the association with type 2 diabetes is slightly weaker. The risk allele KCNJ11 (G) and the protective allele PPAR? (G) are virtually absent. The potential influence of comparatively rare CAPN10 haplotypes on type 2 diabetes risk in this population requires further evaluation. Large-scale genetic studies among native Africans aiming at fine-mapping the candidate genes are needed to identify the actual factors involved in their increased susceptibility to type 2 diabetes.

SUBMITTER: Danquah I

PROVIDER: S-EPMC3848778 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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The TCF7L2 rs7903146 (T) allele is associated with type 2 diabetes in urban Ghana: a hospital-based case-control study.

Danquah Ina I Othmer Till T Frank Laura K LK Bedu-Addo George G Schulze Matthias B MB Mockenhaupt Frank P FP

BMC medical genetics 20130923

<h4>Background</h4>Type 2 diabetes mellitus is increasing dramatically in sub-Saharan Africa, and genetic predisposition is likely involved in that. Yet, genetic variants known to confer increased susceptibility among Caucasians are far from being established in African populations. In Ghanaian adults, we examined associations of several of these polymorphisms with type 2 diabetes.<h4>Methods</h4>A hospital-based case-control study on type 2 diabetes (and hypertension) was conducted in Kumasi, G ...[more]

PMID: 24059590

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Project description:Hereditary Multiple Exostoses (HME) is an autosomal-dominant disorder characterized by benign cartilage tumors (exostoses) forming near the growth plates, leading to severe health problems. EXT1 and EXT2 are the two genes known to harbor heterozygous loss-of-function mutations that account for the vast majority of the primary genetic component of HME. However, patients present with wide clinical heterogeneity, suggesting that modifier genes play a role in determining severity. Our previous work has pointed to an imbalance of ?-catenin signaling being involved in the pathogenesis of osteochondroma formation. TCF7L2 is one of the key 'gate-keeper' TCF family members for Wnt/?-catenin signaling pathway, and TCF7L2 and EXT2 are among the earliest associated loci reported in genome wide appraisals of type 2 diabetes (T2D). Thus we investigated if the key T allele of single nucleotide polymorphism (SNP) rs7903146 within the TCF7L2 locus, which is strongly over-represented among T2D cases, was also associated with HME. We leveraged genotype data available from ongoing GWAS efforts from genomics and orthopedic centers in the US, Canada and Italy. Collectively 213 cases and 1890 controls were analyzed and, surprisingly, the T allele was in fact significantly under-represented in the HME patient group [P = 0.009; odds ratio = 0.737 (95% C.I. 0.587-0.926)]; in addition, the direction of effect was consistent within each individual cohort. Immunohistochemical analyses revealed that TCF7L2 is differentially expressed and distributed in normal human growth plate zones, and exhibits substantial variability in human exostoses in terms of staining intensity and distribution. In summary, the data indicate that there is a putative genetic connection between TCF7L2 and EXT in the context of HME. Given this observation, we suggest that these loci could possibly modulate shared pathways, in particular with respect to ?-catenin, and their respective variants interplay to influence HME pathogenesis as well as T2D.

Dataset Information

The TCF7L2 rs7903146 (T) allele is associated with type 2 diabetes in urban Ghana: a hospital-based case-control study.

Publications

The TCF7L2 rs7903146 (T) allele is associated with type 2 diabetes in urban Ghana: a hospital-based case-control study.

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