title: Genetic variants of IDE-KIF11-HHEX at 10q23.33 associated with type 2 diabetes risk: a fine-mapping study in Chinese population.
abstract: BACKGROUND
  Genome-wide association studies (GWAS) in populations of European ancestry have mapped a type 2 diabetes susceptibility region to chromosome 10q23.33 containing IDE, KIF11 and HHEX genes (IDE-KIF11-HHEX), which has also been replicated in Chinese populations. However, the functional relevance for genetic variants at this locus is still unclear. It is critical to systematically assess the relationship of genetic variants in this region with the risk of type 2 diabetes.
  
  
  RESULTS
  A fine-mapping study was conducted by genotyping fourteen tagging single-nucleotide polymorphisms (SNPs) in a 290-kb linkage disequilibrium (LD) region using a two-stage case-control study of type 2 diabetes in a Chinese Han population. Suggestive associations (P<0.05) observed from 1,200 cases and 1,200 controls in the first stage were further replicated in 1,725 cases and 2,081 controls in the second stage. Seven tagging SNPs were consistently associated with type 2 diabetes in both stages (P<0.05), with combined odds ratios (ORs) ranging from 1.14 to 1.33 in the combined analysis. The most significant locus was rs7923837 [OR = 1.33, 95% confidence interval (CI): 1.21-1.47] at the 3'-flanking region of HHEX gene. SNP rs1111875 was found to be another partially independent locus (OR = 1.23, 95% CI: 1.13-1.35) in this region that was associated with type 2 diabetes risk. A cumulative effect of rs7923837 and rs1111875 was observed with individuals carrying 1, 2, and 3 or 4 risk alleles having a 1.27, 1.44, and 1.73-fold increased risk, respectively, for type 2 diabetes (P for trend = 4.1E-10).
  
  
  CONCLUSIONS
  Our results confirm that genetic variants of the IDE-KIF11-HHEX region at 10q23.33 contribute to type 2 diabetes susceptibility and suggest that rs7923837 may represent the strongest signal related to type 2 diabetes risk in the Chinese Han population.
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China. yunqian@yahoo.cn
authors.forename: Yun
authors.initials: Y
authors.lastname: Qian
authors.forename: Feng
authors.initials: F
authors.lastname: Lu
authors.forename: Meihua
authors.initials: M
authors.lastname: Dong
authors.forename: Yudi
authors.initials: Y
authors.lastname: Lin
authors.forename: Huizhang
authors.initials: H
authors.lastname: Li
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.forename: Chong
authors.initials: C
authors.lastname: Shen
authors.forename: Guangfu
authors.initials: G
authors.lastname: Jin
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Hu
authors.forename: Hongbing
authors.initials: H
authors.lastname: Shen
mesh_terms: D000483:Alleles; D044466:Asian People; D016022:Case-Control Studies; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D016547:Kinesins / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C078492:HHEX protein, human; D018398:Homeodomain Proteins; C470243:KIF11 protein, human; D014157:Transcription Factors; D016547:Kinesins