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

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.

Figure

Plots of T2D association signals in KCNQ1 (Panel A) and KCNJ11/ABCC8 (Panel B) genes detected in the Mongolian population. P-values for the association (in −log₁₀ scale) are shown for each SNP as diamonds and plotted according to their location on chromosome 11. The strongest P-values for 3 SNPs in KCNQ1 (rs2237892, rs2237895, and rs2237897) and 2 SNPs in ABCC8 (rs1799858 and rs2074308) overcame the P-value threshold adjusted for multiple testing (P=0.0024).