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

Danquah, Ina; Othmer, Till; Frank, Laura; Bedu-Addo, George; Schulze, Matthias B.; Mockenhaupt, Frank P.

doi:10.1186/1471-2350-14-96

Cited by 41 publications

(31 citation statements)

References 35 publications

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“…While this is the case in other population groups, some studies reported a weak 33,34 or no association [35][36][37][38] . Other studies highlighted the effect of the TCF7L2 polymorphisms on the progression of T2DM 35,39 , in some ethnic population groups these variants were associated with responses to medication 40,41 , and in others their effect on the disease was modulated by the type of diet [42][43][44] .Our results [1.43 (1.00 to 2.04), p= 0.053] are comparable to those reported for other African ethnic population groups 17,18,20 . It is possible that TCF7L2 polymorphisms have different effects in various ethnic population groups depending on the diet.…”

Section: Discussionsupporting

confidence: 78%

“…Although few number of T2DM susceptibility genes discovered through candidate gene, linkage analyses, and GWA studies elsewhere have been replicated in African studies [16][17][18][19][20][21] , it must also be emphasized that many other association studies failed to show significant and replicable findings [22][23][24] . Therefore in this study we investigated three genes, namely, TCF7L2, FTO, and ENPP1 as risk factors for T2DM in a South African ethnic population group of Mixed-ancestry (Coloureds) with a unique genetic architecture.…”

Section: Introductionmentioning

confidence: 99%

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Contribution of ENPP1, TCF7L2, and FTO polymorphisms to type 2 diabetes in mixed ancestry ethnic population of South Africa

et al. 2016

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Background: Transcription factor 7-like 2 gene (TCF7L2), fat mass and obesity-associated gene (FTO), and ectonucleotide pyrophosphatase/phosphodiesterase gene (ENPP1) are known risk loci for type 2 diabetes (T2DM) mostly in European populations. Objectives: To assess the association of these genes with T2DM risk in a South African mixed-ancestry population. Methods: Five hundred and sixty six participants were genotyped for ENPP1-rs997509 and -rs1044498, FTO-9941349 and -rs3751812, TCF7L2-rs12255372 and -rs7903146 polymorphisms using Taqman genotyping assays and validated by automated sequencing to assess the association of the polymorphisms with cardiometabolic traits. Results: In logistic regression models adjusted for age, sex, body mass index (BMI) and insulin resistance, minor allele of rs997509 was associated with a higher risk of prevalent T2DM under a recessive model [odd ratio 4.60 (95% confidence interval: 1.07 to 19.86); p = 0.040].Under additive model, the rs7903146 [1.43 (1.00 to 2.04); p= 0.053] and rs9941349 [1.43 (1.00 to 2.04); p = 0.052] minor alleles showed marginally significant associations with a high risk of T2DM. However, only the rs7903146 alleles (p=0.011) and genotypes (p=0.025) distributions were statistically significantly different between diabetic and non-diabetic individuals. Conclusion: Our findings demonstrate that ENPP1, TCF7L2, and FTO may predispose to T2DM in the mixed-ancestry population.

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Section: Discussionsupporting

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Contribution of ENPP1, TCF7L2, and FTO polymorphisms to type 2 diabetes in mixed ancestry ethnic population of South Africa

et al. 2016

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“…rs7903146 was genome-wide significant as expected from previous T2D studies in Africa 4,[20][21][22][23][24][25] and consistent with the findings of most populations studied around the world. We also replicated several previously reported T2D loci.…”

Section: Discussionsupporting

confidence: 89%

A Novel Type 2 Diabetes Locus in sub-Saharan Africans, ZRANB3, is Implicated in Beta Cell Proliferation

Adeyemo

Chen

Doumatey

et al. 2019

Preprint

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Genome analysis of diverse human populations has contributed to the identification of novel genomic loci for diseases of major clinical and public health impact. Here, we report the largest genome-wide analysis of type 2 diabetes (T2D) in sub-Saharan Africans, an understudied ancestral group. We analyzed ~18 million autosomal SNPs in 5,231 individuals from Nigeria, Ghana and Kenya. TCF7L2 rs7903156 was the most significant locus (p=7.288 X 10 -13 ). We identified a novel genome wide significant locus: ZRANB3 (Zinc Finger RANBP2-Type Containing 3, lead SNP chr2:136064024, T allele frequency=0.034, p=2.831x10 -9 ). Knockdown of the zebrafish ortholog resulted in reduction in pancreatic beta cell number in the developing organism, suggesting a potential mechanism for its effect on glucose hemostasis. We also showed transferability in our study of 32 established T2D loci. Our findings provide evidence of a novel candidate T2D locus and advance understanding of the genetics of T2D in non-European ancestry populations.

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“…After the initial report on the association of a common microsatellite within intron 3 of TCF7L2 (DG10S478) with T2DM (14), successive replication studies conducted in populations of different ethnic origin confirmed the strong association between a number of TCF7L2 polymorphisms, especially rs7903146 and rs12255372, and T2DM (15)(16)(17)(18)(19)(20)(21)(22). Moreover, among Latin American countries there are only reports on the association of TCF7L2 polymorphisms and T2DM from Colombia (23), Brazil (24)(25)(26)(27)(28) and Mexico (9,(29)(30)(31)(32).…”

Section: Tcf7l2 Polymorphisms and Type 2 Diabetes Riskmentioning

confidence: 99%

Design of an allele-specific PCR assay to genotype the rs12255372 SNP in a pilot study of association between common TCF7L2 polymorphisms and type 2 diabetes in Venezuelans

Moran

Labrador

Camargo

et al. 2016

Arch. Endocrinol. Metab.

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Objective: The global burden of diabetes mellitus will impact strongly American countries in the coming decades. Type 2 diabetes mellitus (T2DM) is a multifactorial disease and the basis for its genetic susceptibility remains not fully understood. Different population studies have demonstrated that variants of the TCF7L2 gene are strongly associated with an increased risk of T2DM. Moreover, institutions or countries with limited budget to conduct genetic research need cost effective methods for detecting DNA variants. Subjects and methods: We standardized a rapid and simple allele-specific PCR method for genotyping the rs12255372 single nucleotide polymorphism (SNP) in a pilot study exploring the association of three TCF7L2 polymorphisms (rs7903146, rs12255372 and DG10S478) with T2DM in 70 patients and 73 controls from Venezuela. Results: The performance of the designed allele-specific PCR reaction for rs12255372 genotyping was reliable and accurate. Patients carrying the TCF7L2 rs7903146 T allele (CT + TT genotypes) and heterozygous CT genotype had a significantly higher risk for T2DM (OR = 2.9 and 2.3, respectively). Although rs12255372 and DG10S478 risk alleles predominated in T2DM group no statistical significance was found. Conclusions: We developed a novel allele-specific PCR method for easier and rapid detection of rs12255372 polymorphism without the use of expensive instrumentation and reagents. Our study in a relatively small sample of the Venezuelan population replicated the association of the rs7903146 SNP with T2DM. Further studies with larger sample size and more biochemical data should be conducted to explore the genetic basis of T2DM susceptibility in Venezuela. Arch Endocrinol Metab. 2016;60(3):246-51

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

Cited by 41 publications

References 35 publications

Contribution of ENPP1, TCF7L2, and FTO polymorphisms to type 2 diabetes in mixed ancestry ethnic population of South Africa

Contribution of ENPP1, TCF7L2, and FTO polymorphisms to type 2 diabetes in mixed ancestry ethnic population of South Africa

A Novel Type 2 Diabetes Locus in sub-Saharan Africans, ZRANB3, is Implicated in Beta Cell Proliferation

Design of an allele-specific PCR assay to genotype the rs12255372 SNP in a pilot study of association between common TCF7L2 polymorphisms and type 2 diabetes in Venezuelans

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