Variations in/nearby genes coding for JAZF1, TSPAN8/LGR5 and HHEX-IDE and risk of type 2 diabetes in Han Chinese

J Hum Genet. 2010 Dec;55(12):810-5. doi: 10.1038/jhg.2010.117. Epub 2010 Oct 7.

Abstract

Several genetic loci (JAZF1, CDC123/CAMK1D, TSPAN8/LGR5, ADAMTS9, VEGFA and HHEX-IDE) were identified to be significantly related to the risk of type 2 diabetes and quantitative metabolic traits in European populations. Here, we aimed to evaluate the impacts of these novel loci on type 2 diabetes risk in a population-based case-control study of Han Chinese (1912 cases and 2041 controls). We genotyped 13 single-nucleotide polymorphisms (SNPs) in/near these genes and examined the differences in allele/genotype frequency between cases and controls. We found that both IDE rs11187007 and HHEX rs1111875 were associated with type 2 diabetes risk (for both variants: odds ratio (OR)=1.15, 95% confidence interval (CI) 1.04-1.28, P=0.009). In a meta-analysis where we pooled our data with the three previous studies conducted in East Asians, we found that the variants of JAZF1 rs864745 (1.09 (1.03-1.16); P=3.49 × 10(-3)) and TSPAN8/LGR5 rs7961581 (1.11(1.05-1.17); P=1.89 × 10(-4)) were significantly associated with type 2 diabetes risk. In addition, the meta-analysis (7207 cases and 8260 controls) also showed that HHEX rs1111875 did have effects on type 2 diabetes in Chinese population (OR=1.15(1.10-1.21); P=1.93 × 10(-8)). This large population-based study and meta-analysis further confirmed the modest effects of the JAZF1, TSPAN8/LGR5 and HHEX-IDE loci on type 2 diabetes in Chinese and other East Asians.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antigens, Neoplasm / genetics*
  • Asian People / genetics
  • China / epidemiology
  • Chromosomes, Human, Pair 10 / genetics
  • Chromosomes, Human, Pair 12 / genetics
  • Chromosomes, Human, Pair 3 / genetics
  • Chromosomes, Human, Pair 6 / genetics
  • Chromosomes, Human, Pair 7 / genetics
  • Co-Repressor Proteins
  • DNA-Binding Proteins
  • Diabetes Mellitus, Type 2 / epidemiology*
  • Diabetes Mellitus, Type 2 / genetics*
  • Female
  • Gene Frequency
  • Genetic Loci
  • Genetic Variation
  • Homeodomain Proteins / genetics*
  • Humans
  • Membrane Glycoproteins / genetics*
  • Middle Aged
  • Neoplasm Proteins / genetics*
  • Polymorphism, Single Nucleotide
  • Receptors, G-Protein-Coupled / genetics*
  • Risk
  • Tetraspanins
  • Transcription Factors / genetics*

Substances

  • Antigens, Neoplasm
  • Co-Repressor Proteins
  • DNA-Binding Proteins
  • HHEX protein, human
  • Homeodomain Proteins
  • JAZF1 protein, human
  • LGR5 protein, human
  • Membrane Glycoproteins
  • Neoplasm Proteins
  • Receptors, G-Protein-Coupled
  • TSPAN8 protein, human
  • Tetraspanins
  • Transcription Factors