title: Variants from GIPR, TCF7L2, DGKB, MADD, CRY2, GLIS3, PROX1, SLC30A8 and IGF1 are associated with glucose metabolism in the Chinese.
abstract: BACKGROUND
  Recent meta-analysis of genome-wide association studies in European descent samples identified novel loci influencing glucose and insulin related traits. In the current study, we aimed to evaluate the association between these loci and traits related to glucose metabolism in the Chinese.
  
  
  RESULTS
  We genotyped seventeen single nucleotide polymorphisms (SNPs) from fifteen loci including GIPR, ADCY5, TCF7L2, VPS13C, DGKB, MADD, ADRA2A, FADS1, CRY2, SLC2A2, GLIS3, PROX1, C2CD4B, SLC30A8 and IGF1 in 6,822 Shanghai Chinese Hans comprising 3,410 type 2 diabetic patients and 3,412 normal glucose regulation subjects. MADD rs7944584 showed strong association to type 2 diabetes (p = 3.5×10(-6), empirical p = 0.0002) which was not observed in the European descent populations. SNPs from GIPR, TCF7L2, CRY2, GLIS3 and SLC30A8 were also associated with type 2 diabetes (p = 0.0487∼2.0×10(-8)). Further adjusting age, gender and BMI as confounders found PROX1 rs340874 was associated with type 2 diabetes (p = 0.0391). SNPs from DGKB, MADD and SLC30A8 were associated with fasting glucose while PROX1 rs340874 was significantly associated with OGTT 2-h glucose (p = 0.0392∼0.0014, adjusted for age, gender and BMI), the glucose-raising allele also showed association to lower insulin secretion. IGF1 rs35767 showed significant association to both fasting and 2-h insulin levels as well as insulin secretion and sensitivity indices (p = 0.0160∼0.0035, adjusted for age, gender and BMI).
  
  
  CONCLUSIONS
  Our results indicated that SNPs from GIPR, TCF7L2, DGKB, MADD, CRY2, GLIS3, PROX1, SLC30A8 and IGF1 were associated with traits related to glucose metabolism in the Chinese population.
authors.affiliation: Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, People's Republic of China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Hu
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.forename: Congrong
authors.initials: C
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Ma
authors.forename: Xuhong
authors.initials: X
authors.lastname: Hou
authors.forename: Jingyi
authors.initials: J
authors.lastname: Lu
authors.forename: Weihui
authors.initials: W
authors.lastname: Yu
authors.forename: Feng
authors.initials: F
authors.lastname: Jiang
authors.forename: Yuqian
authors.initials: Y
authors.lastname: Bao
authors.forename: Kunsan
authors.initials: K
authors.lastname: Xiang
authors.forename: Weiping
authors.initials: W
authors.lastname: Jia
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D001786:Blood Glucose / Q000378:metabolism; D027682:Cation Transport Proteins; D002681:China; D053418:Death Domain Receptor Signaling Adaptor Proteins; D000090943:Delta-5 Fatty Acid Desaturase; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000208:ethnology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods*; D005838:Genotype; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D020662:Guanine Nucleotide Exchange Factors; D018398:Homeodomain Proteins; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D025521:Tumor Suppressor Proteins; D000075703:Zinc Transporter 8; D000098551:Prospero-Related Homeobox 1 Protein
chemical_list: D001786:Blood Glucose; D027682:Cation Transport Proteins; D053418:Death Domain Receptor Signaling Adaptor Proteins; D000090943:Delta-5 Fatty Acid Desaturase; D020662:Guanine Nucleotide Exchange Factors; D018398:Homeodomain Proteins; D007328:Insulin; C105852:MADD protein, human; C492522:SLC30A8 protein, human; D025521:Tumor Suppressor Proteins; D000075703:Zinc Transporter 8; D000098551:Prospero-Related Homeobox 1 Protein; C000716847:FADS1 protein, human; D005947:Glucose