Genetic variants in potassium channels are associated with type 2 diabetes in a Mongolian population

J Diabetes. 2012 Sep;4(3):238-42. doi: 10.1111/j.1753-0407.2011.00177.x.

Abstract

Background: Recent genome-wide association studies (GWAS) have identified more than 40 common sequence variants associated with type 2 diabetes (T2D). However, the results are not always the same in populations with differing genetic backgrounds. In the present study, we evaluated a hypothesis that a North Asian population living in a geographic area with unusually harsh environmental conditions would develop unique genetic risks.

Methods: A population-based association study was performed with 21 single-nucleotide polymorphisms (SNPs) in nine genes selected according to the results of GWAS conducted in other populations. The study participants included 393 full-heritage Mongolian individuals (177 diagnosed with T2D and 216 matched controls). Genotyping was performed by TaqMan methodology.

Results: The strongest association was detected with SNPs located within the potassium channel-coding genes KCNQ1 (highest odds ratio [OR] = 1.92; P = 3.4 × 10(-5) ) and ABCC8 (OR = 1.79; P = 5 × 10(-4) ). Genetic variants identified as strongly influencing the risk of T2D in other populations (e.g. KCNJ11 or TCF7L2) did not show significant association in Mongolia.

Conclusions: The strongest T2D risk-associated SNPs in Mongolians are located within two of three tested potassium channel-coding genes. Accumulated variations in these genes may be related to the exposure to harsh environmental conditions.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • ATP-Binding Cassette Transporters / genetics
  • Alleles
  • Diabetes Mellitus, Type 2 / genetics*
  • Gene Frequency
  • Gene-Environment Interaction
  • Genetic Predisposition to Disease / genetics*
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Introns / genetics
  • KCNQ1 Potassium Channel / genetics*
  • Linkage Disequilibrium
  • Middle Aged
  • Mongolia
  • Polymorphism, Single Nucleotide*
  • Potassium Channels, Inwardly Rectifying / genetics
  • Receptors, Drug / genetics
  • Risk Factors
  • Sulfonylurea Receptors

Substances

  • ATP-Binding Cassette Transporters
  • KCNQ1 Potassium Channel
  • KCNQ1 protein, human
  • Potassium Channels, Inwardly Rectifying
  • Receptors, Drug
  • Sulfonylurea Receptors