title: Variants in GLIS3 and CRY2 are associated with type 2 diabetes and impaired fasting glucose in Chinese Hans.
abstract: BACKGROUND
  Recent genome-wide association studies have identified a number of common variants associated with fasting glucose homeostasis and type 2 diabetes in populations of European origin. This is a replication study to examine whether such associations are also observed in Chinese Hans.
  
  
  METHODS
  We genotyped nine variants in or near MADD, ADRA2A, CRY2, GLIS3, PROX1, FADS1, C2CD4B, IGF1 and IRS1 in a population-based cohort including 3,210 unrelated Chinese Hans from Beijing and Shanghai.
  
  
  RESULTS
  We confirmed the associations of GLIS3-rs7034200 with fasting glucose (beta = 0.07 mmol/l, P = 0.03), beta cell function (HOMA-B) (beta = -3.03%, P = 0.009), and type 2 diabetes (OR [95%CI]  = 1.27 [1.09-1.49], P = 0.003) after adjustment for age, sex, region and BMI. The association for type 2 diabetes remained significant after adjusting for other diabetes related risk factors including family history of diabetes, lipid profile, medication information, hypertension and life style factors, while further adjustment for HOMA-B abolished the association. The A-allele of CRY2-rs11605924 was moderately associated with increased risk of combined IFG/type 2 diabetes (OR [95%CI]  = 1.15[1.01-1.30], P = 0.04). SNPs in or near MADD, ADRA2A, PROX1, FADS1, C2CD4B, IGF1, and IRS1 did not exhibit significant associations with type 2 diabetes or related glycemic traits (P≥0.10).
  
  
  CONCLUSIONS
  In conclusion, our results indicate the associations of GLIS3 locus with type 2 diabetes and impaired fasting glucose in Chinese Hans, partially mediated through impaired beta-cell function. In addition, we also found modest evidence for the association of CRY2-rs11605924 with combined IFG/type 2 diabetes.
authors: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Graduate School of the Chinese Academy of Sciences, Shanghai, China.
authors: Chen
authors: C
authors: Liu
authors: Huaixing
authors: H
authors: Li
authors: Lu
authors: L
authors: Qi
authors: Ruth J F
authors: RJ
authors: Loos
authors: Qibin
authors: Q
authors: Qi
authors: Ling
authors: L
authors: Lu
authors: Wei
authors: W
authors: Gan
authors: Xu
authors: X
authors: Lin
mesh_terms: D000368:Aged; D044466:Asian People / Q000235:genetics*; D001786:Blood Glucose / Q000378:metabolism*; D002681:China / Q000208:ethnology; D056931:Cryptochromes / Q000235:genetics*; D004268:DNA-Binding Proteins; D000090943:Delta-5 Fatty Acid Desaturase; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics*; D005215:Fasting / Q000097:blood*; D005260:Female; D056426:Genetic Loci / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D001786:Blood Glucose; C538966:CRY2 protein, human; D056931:Cryptochromes; D004268:DNA-Binding Proteins; D000090943:Delta-5 Fatty Acid Desaturase; C512851:GLIS3 protein, human; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C000716847:FADS1 protein, human