title: Transcription factor-7-like 2 gene variants are strongly associated with type 2 diabetes in Tunisian Arab subjects.
abstract: Genome-wide association studies validated transcription factor 7-like 2 (TCF7L2) gene as confirmed type 2 diabetes (T2DM) susceptibility locus, and an ethnic contribution of TCF7L2 variants to T2DM risk was indicated. The aim of this study was to replicate in a Tunisian Arab population identified associations of common TCF7L2 variants with T2DM. We tested the association of TCF7L2 variants: rs4506565, rs7903146, rs12243326, and rs12255372, with T2DM in 900 Tunisian patients and 875 control subjects. TCF7L2 genotyping was done by allelic discrimination/real-time PCR method. Minor allele frequencies of rs4506565 (P=2.4×10(-8)), rs7903146 (P=1.2×10(-6)), rs12243326 (P=8.4×10(-8)) and rs12255372 (P=1.1×10(-5)) were significantly higher in cases. The four tested TCF7L2 variants were in linkage disequilibrium, and 4-locus (rs4506565, rs7903146, rs12243326, rs12255372) haplotype analysis demonstrated that haplotype 1111 was negatively associated (Pc<0.001), while haplotypes 2222 (Pc=0.008) and 2211 (Pc=0.020) were positively associated with T2DM risk, after controlling for a number of covariates. The strong contribution of TCF7L2 gene variants to T2DM among Tunisians is in line with similar findings in other ethnic groups, confirming TCF7L2 as a common T2DM candidate gene.
authors.affiliation: Faculty of Pharmacy of Monastir, University of Monastir, Monastir, Tunisia.
authors.forename: Amira
authors.initials: A
authors.lastname: Turki
authors.forename: Ghadeer S
authors.initials: GS
authors.lastname: Al-Zaben
authors.forename: Nabil
authors.initials: N
authors.lastname: Mtiraoui
authors.forename: Hela
authors.initials: H
authors.lastname: Marmmuoch
authors.forename: Touhami
authors.initials: T
authors.lastname: Mahjoub
authors.forename: Wassim Y
authors.initials: WY
authors.lastname: Almawi
mesh_terms: D000368:Aged; D018912:Arabs / Q000235:genetics; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D058118:Transcription Factor 7-Like 2 Protein / Q000235:genetics*; D014416:Tunisia
chemical_list: C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein