title: Contribution of ENPP1, TCF7L2, and FTO polymorphisms to type 2 diabetes in mixed ancestry ethnic population of South Africa.
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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  Our findings demonstrate that ENPP1, TCF7L2, and FTO may predispose to T2DM in the mixed-ancestry population.
authors.affiliation: Department of Surgery, Faculty of Health Sciences, University of Witwatersrand, South Africa.
authors.forename: Yandiswa Y
authors.initials: YY
authors.lastname: Yako
authors.affiliation: Department of Biomedical Sciences Faculty of Health and Wellness Sciences, Cape Peninsula University of Technology, Cape Town, South Africa.
authors.forename: Jabulisile H
authors.initials: JH
authors.lastname: Madubedube
authors.affiliation: 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.
authors.forename: Andre P
authors.initials: AP
authors.lastname: Kengne
authors.affiliation: Division of Chemical Pathology, Faculty of Medicine and Health Sciences, National Health Laboratory Service (NHLS) and University of Stellenbosch, Cape Town, South Africa.
authors.forename: Rajiv T
authors.initials: RT
authors.lastname: Erasmus
authors.affiliation: Institute for Cellular and Molecular Medicine, Molecular Endocrinology, University of Pretoria.
authors.forename: Tahir S
authors.initials: TS
authors.lastname: Pillay
authors.affiliation: Department of Biomedical Sciences Faculty of Health and Wellness Sciences, Cape Peninsula University of Technology, Cape Town, South Africa.
authors.forename: Tandi E
authors.initials: TE
authors.lastname: Matsha
mesh_terms: D000483:Alleles; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO / Q000235:genetics*; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology* / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D010727:Phosphoric Diester Hydrolases / Q000235:genetics*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011755:Pyrophosphatases / Q000235:genetics*; D013019:South Africa; D019914:Taq Polymerase; D058118:Transcription Factor 7-Like 2 Protein / Q000235:genetics*
chemical_list: D058118:Transcription Factor 7-Like 2 Protein; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human; D019914:Taq Polymerase; D010727:Phosphoric Diester Hydrolases; C065962:ectonucleotide pyrophosphatase phosphodiesterase 1; D011755:Pyrophosphatases
keywords: Africa; ENPP1; FTO; TCF7L2; Type 2 diabetes; genetics