Yandiswa Y Yako1, Jabulisile H Madubedube2, Andre P Kengne3, Rajiv T Erasmus4, Tahir S Pillay5, Tandi E Matsha2. 1. Department of Surgery, Faculty of Health Sciences, University of Witwatersrand, South Africa. 2. Department of Biomedical Sciences Faculty of Health and Wellness Sciences, Cape Peninsula University of Technology, Cape Town, South Africa. 3. Non-Communicable Diseases Research Unit, South African Medical Research Council, Cape Town, South Africa; Department of Medicine, University of Cape Town, Cape Town, South Africa. 4. Division of Chemical Pathology, Faculty of Medicine and Health Sciences, National Health Laboratory Service (NHLS) and University of Stellenbosch, Cape Town, South Africa. 5. Institute for Cellular and Molecular Medicine, Molecular Endocrinology, University of Pretoria.
Abstract
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.
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.
Entities:
Keywords:
Africa; ENPP1; FTO; TCF7L2; Type 2 diabetes; genetics
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