title: Association of genetic variants with isolated fasting hyperglycaemia and isolated postprandial hyperglycaemia in a Han Chinese population.
abstract: BACKGROUND
  Though multiple single nucleotide polymorphisms (SNPs) associated with type 2 diabetes have been identified, the genetic bases of isolated fasting hyperglycaemia (IFH) and isolated postprandial hyperglycaemia (IPH) were still unclear. In present study, we aimed to investigate the association of genome-wide association study-validated genetic variants and IFH or IPH in Han Chinese.
  
  
  RESULTS
  We genotyped 27 validated SNPs in 6,663 unrelated individuals comprising 341 IFH, 865 IPH, 1,203 combined fasting hyperglycaemia and postprandial hyperglycaemia, and 4,254 normal glycaemic subjects of Han ancestry. The distributions of genotype frequencies of FTO, CDKAL1 and GCKR were significant different between individuals with IFH and those with IPH (SNP(ptrend ): rs8050136(0.0024), rs9939609(0.0049), rs7756992(0.0122), rs780094(0.0037)). Risk allele of FTO specifically increased the risk of IFH (rs8050136: OR 1.403 [95% CI 1.125-1.750], p = 0.0027; rs9939609: 1.398 [1.120-1.744], p = 0.0030). G allele of CDKAL1 specifically increased the risk of IPH (1.217 [1.092-1.355], p = 0.0004). G allele of GCKR increased the risk of IFH (1.167 [0.999-1.362], p = 0.0513), but decreased the risk of IPH (0.891 [0.801-0.991], p = 0.0331). In addition, TCF7L2 and KCNQ1 increased the risk of both IFH and IPH. When combined, each additional risk allele associated with IFH increased the risk for IFH by 1.246-fold (p<0.0001), while each additional risk allele associated with IPH increased the risk for IPH by 1.190-fold (p<0.0001).
  
  
  CONCLUSIONS
  Our results indicate that genotype distributions of variants from FTO, GCKR, CDKAL1 were different between IPH and IFH in Han Chinese. Variants of genes modulating insulin sensitivity (FTO, GCKR) contributed to the risk of IFH, while variants of genes related to beta cell function (CDKAL1) increase the risk of IPH.
authors.affiliation: Department of Endocrinology, Key Laboratory of Diabetes Prevention and Control, China-Japan Friendship Hospital, Beijing, China.
authors.forename: Xiaomu
authors.initials: X
authors.lastname: Kong
authors.forename: Jing
authors.initials: J
authors.lastname: Hong
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Zhao
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.forename: Jiapu
authors.initials: J
authors.lastname: Ge
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Guo
authors.forename: Juming
authors.initials: J
authors.lastname: Lu
authors.forename: Jianping
authors.initials: J
authors.lastname: Weng
authors.forename: Weiping
authors.initials: W
authors.lastname: Jia
authors.forename: Linong
authors.initials: L
authors.lastname: Ji
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Xiao
authors.forename: Zhongyan
authors.initials: Z
authors.lastname: Shan
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Haoming
authors.initials: H
authors.lastname: Tian
authors.forename: Qiuhe
authors.initials: Q
authors.lastname: Ji
authors.forename: Dalong
authors.initials: D
authors.lastname: Zhu
authors.forename: Zhiguang
authors.initials: Z
authors.lastname: Zhou
authors.forename: Guangliang
authors.initials: G
authors.lastname: Shan
authors.forename: Wenying
authors.initials: W
authors.lastname: Yang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000328:Adult; D000368:Aged; D000483:Alleles; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D000886:Anthropometry; D044466:Asian People / Q000235:genetics; D001786:Blood Glucose / Q000235:genetics; D002681:China; D015331:Cohort Studies; D051360:Cyclin-Dependent Kinase 5 / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000235:genetics*; D005215:Fasting; D005260:Female; D005819:Genetic Markers; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D006943:Hyperglycemia / Q000208:ethnology / Q000235:genetics*; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000166:cytology; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D019518:Postprandial Period; D011506:Proteins / Q000235:genetics; D012306:Risk; D012359:tRNA Methyltransferases
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D001786:Blood Glucose; C485100:GCKR protein, human; D005819:Genetic Markers; D007328:Insulin; D011506:Proteins; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human; D012359:tRNA Methyltransferases; D051360:Cyclin-Dependent Kinase 5; C525110:CDKAL1 protein, human