Contribution of common variants of ENPP1 , IGF2BP2 , KCNJ11 , MLXIPL , PPARγ , SLC30A8 and TCF7L2 to the risk of type 2 diabetes in Lebanese and Tunisian Arabs

• Published in: Diabetes & metabolism 2012-11, Vol.38 (5), p.444-449
• Main Authors: Mtiraoui, N, Turki, A, Nemr, R, Echtay, A, Izzidi, I, Al-Zaben, G.S, Irani-Hakime, N, Keleshian, S.H, Mahjoub, T, Almawi, W.Y
• Format: Article
• Language: English
• Subjects: Arab population; Arabs - genetics; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - genetics; Biological and medical sciences; Body Mass Index; Cation Transport Proteins - genetics; Diabetes Mellitus, Type 2 - epidemiology; Diabetes Mellitus, Type 2 - ethnology; Diabetes Mellitus, Type 2 - genetics; Diabetes. Impaired glucose tolerance; Diabète de type 2; Endocrine pancreas. Apud cells (diseases); Endocrinology & Metabolism; Endocrinopathies; ENPP1; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Genetic Predisposition to Disease; Genetics; Genome-wide association studies; Genome-Wide Association Study; Genotype; Glycated Hemoglobin A - metabolism; Génétique; Humans; IGF2BP2; Internal Medicine; KCNJ11; Lebanon; Lebanon - epidemiology; Lebanon - ethnology; Liban; Male; Medical sciences; Middle Aged; MLXIPL; Phosphoric Diester Hydrolases - genetics; Polymorphism, Single Nucleotide; Polymorphismes fréquents; Populations arabes; Potassium Channels, Inwardly Rectifying - genetics; PPAR gamma - genetics; PPARγ; Pyrophosphatases - genetics; RNA-Binding Proteins - genetics; SLC30A8; SNPs; TCF7L2; Transcription Factor 7-Like 2 Protein - genetics; Tunisia; Tunisia - epidemiology; Tunisia - ethnology; Tunisie; Type 2 diabetes
• ISSN: 1262-3636; 1878-1780
• DOI: 10.1016/j.diabet.2012.05.002

Abstract Background While several type 2 diabetes mellitus (T2DM) susceptibility loci identified through genome-wide association studies (GWAS) have been replicated in many populations, their association in Arabs has not been reported. For this reason, the present study looked at the contribution of ENNP1 (rs1044498), IGF2BP2 (rs1470579), KCNJ11 (rs5219), MLXIPL (rs7800944), PPARγ (rs1801282), SLC30A8 (rs13266634) and TCF7L2 (rs7903146) SNPs to the risk of T2DM in Lebanese and Tunisian Arabs. Methods Study subjects (case/controls) were Lebanese (751/918) and Tunisians (1470/838). Genotyping was carried out by the allelic discrimination method. Results In Lebanese and Tunisians, neither ENNP1 nor MLXIPL was associated with T2DM, whereas TCF7L2 was significantly associated with an increased risk of T2DM in both the Lebanese [ P < 0.001; OR (95% CI): 1.38 (1.20–1.59)] and Tunisians [ P < 0.001; OR (95% CI): 1.36 (1.18–1.56)]. Differential associations of IGF2BP2 , KCNJ11 , PPARγ and SLC30A8 with T2DM were noted in the two populations. IGF2BP2 [ P = 1.3 × 10−5 ; OR (95% CI): 1.66 (1.42–1.94)] and PPARγ [ P = 0.005; OR (95% CI): 1.41 (1.10–1.80)] were associated with T2DM in the Lebanese, but not Tunisians, while KCNJ11 [ P = 8.0 × 10−4 ; OR (95% CI): 1.27 (1.09–1.47)] and SLC30A8 [ P = 1.6 × 10−5 ; OR (95% CI): 1.37 (1.15–1.62)] were associated with T2DM in the Tunisians, but not Lebanese, after adjusting for gender and body mass index. Conclusion T2DM susceptibility loci SNPs identified through GWAS showed differential associations with T2DM in two Arab populations, thus further confirming the ethnic contributions of these variants to T2DM susceptibility.