Association of Genetic Variation in KCNQ1 with Type 2 Diabetes in the KORA Surveys

Introduction

Besides variants in the TCF7L2 gene, 20 variants predisposing for type 2 diabetes (T2DM) in Caucasians have been identified in genome wide association (GWA) studies so far [1] [2]. The T2DM locus KCNQ1 (potassium voltage-gated channel, KQT-like subfamily, member 1) emerged from two GWA studies conducted in different independent Asian and Scandinavian populations [3] [4]. Both studies concordantly reported on rs2237895 as one of the polymorphisms that predispose to T2DM, but only Unoki et al. could demonstrate this association in a European sample [3] [4]. KCNQ1 encodes the pore-forming subunit of a voltage-gated K⁺ channel (KvLQT1) that is also expressed in brain, adipose tissues, and pancreas [5].

Many initial reports of disease associations could not be replicated in later studies [6]. Furthermore, probably due to bias and genuine population diversity, almost all initial findings regarding disease associations of genetic polymorphisms overestimated the effects [7]. Therefore, this study was designed to investigate the association of the KNCQ1 gene variant rs2237895 and T2DM in a large population-based sample in Southern Germany. We selected this variant, because of its highly significant association with T2DM in the European study sample in the study by Unoki et al., and because it was found to be associated with T2DM in both GWA studies. In order to better understand its pathogenetic relevance, we also investigated the association between rs2237895 and several glycemic traits.

References

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