Association of genetic variants with isolated fasting hyperglycaemia and isolated postprandial hyperglycaemia in a Han Chinese population

PLoS One. 2013 Aug 19;8(8):e71399. doi: 10.1371/journal.pone.0071399. eCollection 2013.

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.

Methods/principal findings: 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).

Conclusion/significance: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adult
  • Aged
  • Alleles
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • Anthropometry
  • Asian People / genetics
  • Blood Glucose / genetics
  • China
  • Cohort Studies
  • Cyclin-Dependent Kinase 5 / genetics
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / genetics*
  • Fasting
  • Female
  • Genetic Markers
  • Genetic Variation
  • Genotype
  • Humans
  • Hyperglycemia / ethnology
  • Hyperglycemia / genetics*
  • Insulin / metabolism
  • Insulin-Secreting Cells / cytology
  • Male
  • Middle Aged
  • Odds Ratio
  • Polymorphism, Single Nucleotide*
  • Postprandial Period
  • Proteins / genetics
  • Risk
  • tRNA Methyltransferases

Substances

  • Adaptor Proteins, Signal Transducing
  • Blood Glucose
  • GCKR protein, human
  • Genetic Markers
  • Insulin
  • Proteins
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • FTO protein, human
  • tRNA Methyltransferases
  • Cyclin-Dependent Kinase 5
  • CDKAL1 protein, human

Grants and funding

This research project was supported by grants from Chinese Medical Association Foundation and Chinese Diabetes Society (http://www.cma.org.cn/ensite/), National 973 Program (2011CB504001)(http://www.973.gov.cn/), China Postdoctoral Science Foundation Grant (2012M520200)(http://res.chinapostdoctor.org.cn/Program/Main.html). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.