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

Diabetes Metab. 2012 Nov;38(5):444-9. doi: 10.1016/j.diabet.2012.05.002. Epub 2012 Jun 27.

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.

MeSH terms

  • Arabs / genetics*
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics
  • Body Mass Index
  • Cation Transport Proteins / genetics
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetes Mellitus, Type 2 / ethnology
  • Diabetes Mellitus, Type 2 / genetics*
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Genotype
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Lebanon / epidemiology
  • Lebanon / ethnology
  • Male
  • Middle Aged
  • PPAR gamma / genetics
  • Phosphoric Diester Hydrolases / genetics
  • Polymorphism, Single Nucleotide*
  • Potassium Channels, Inwardly Rectifying / genetics
  • Pyrophosphatases / genetics
  • RNA-Binding Proteins / genetics
  • Transcription Factor 7-Like 2 Protein / genetics
  • Tunisia / epidemiology
  • Tunisia / ethnology

Substances

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Cation Transport Proteins
  • Glycated Hemoglobin A
  • IGF2BP2 protein, human
  • Kir6.2 channel
  • MLXIPL protein, human
  • PPAR gamma
  • Potassium Channels, Inwardly Rectifying
  • RNA-Binding Proteins
  • SLC30A1 protein, human
  • TCF7L2 protein, human
  • Transcription Factor 7-Like 2 Protein
  • hemoglobin A1c protein, human
  • Phosphoric Diester Hydrolases
  • ectonucleotide pyrophosphatase phosphodiesterase 1
  • Pyrophosphatases