Role of high-risk variants in the development of impaired glucose metabolism was modified by birth weight in Han Chinese

Diabetes Metab Res Rev. 2015 Nov;31(8):790-5. doi: 10.1002/dmrr.2670. Epub 2015 Aug 18.

Abstract

Background: The aim of this study was to investigate the role of common variants in the genes SLC30A8, KCNQ1, and TCF7L2 in the association between birth weight and increased risk of type 2 diabetes in Han Chinese.

Methods: Seven variants (SLC30A8-rs13266634 and rs2466293; KCNQ1-rs2237895 and rs2074196; and TCF7L2-rs11196218, rs7903146, and rs290487) were genotyped in 1181 individuals born in Peking Union Medical College Hospital from 1921 to 1954 by Taqman allelic discrimination assay. All the subjects were stratified by birth weight into groups of ≥3000 g and <3000 g. Associations of genetic variants with birth weight and with risk of type 2 diabetes and impaired glucose tolerance (together as impaired glucose metabolism) were analysed.

Results: After adjustment for sex, gestational weeks, parity, and maternal age, the G allele of KCNQ1-rs2074196 was associated with higher birth weight (p = 0.032). KCNQ1-rs2074196, rs2234895, and TCF7L2-rs290487 were associated with increased risk of impaired glucose metabolism. However, the associations were modified by size at birth. The associations above were only found in subjects with birth weights greater than (or equal to) 3000 g. In subjects with birth weights less than 3000 g, impaired glucose metabolism was associated with variants SLC30A8-rs2466293 and TCF7L2-rs11196218.

Conclusions: The role of common variants in susceptible genes in the development of impaired glucose metabolism was modified by birth weight in Han Chinese. This provides evidence that genetic variants influence birth weight and are involved in development of type 2 diabetes.

Keywords: Chinese; birth weight; single nucleotide polymorphism; type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Birth Weight / genetics*
  • Cation Transport Proteins / genetics*
  • China
  • Diabetes Mellitus, Type 2 / genetics*
  • Female
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Genotype
  • Glucose Metabolism Disorders / genetics*
  • Humans
  • Infant, Newborn
  • KCNQ1 Potassium Channel / genetics*
  • Male
  • Polymorphism, Single Nucleotide*
  • Transcription Factor 7-Like 2 Protein / genetics*
  • Zinc Transporter 8

Substances

  • Cation Transport Proteins
  • KCNQ1 Potassium Channel
  • KCNQ1 protein, human
  • SLC30A8 protein, human
  • TCF7L2 protein, human
  • Transcription Factor 7-Like 2 Protein
  • Zinc Transporter 8