Jafar-Mohammadi, B2; Groves, C J2; Gjesing, A P2; Herrera, B M2; Winckler, W2; Stringham, H M2; Morris, A P2; Lauritzen, Torsten4; Doney, A S F2; Morris, A D2; Weedon, M N2; Swift, A J2; Kuusisto, J2; Laakso, M2; Altshuler, D2; Hattersley, A T2; Collins, F S2; Boehnke, M2; Hansen, T2; Pedersen, O2; Palmer, C N A2; Frayling, T M2; Gloyn, A L2; McCarthy, M I2
1 Institute of General Medical Practice, Faculty of Health Sciences, Aarhus University, Aarhus University2 unknown3 Department of Public Health - Institute of General Medical Practice, Department of Public Health, Health, Aarhus University4 Department of Public Health - Institute of General Medical Practice, Department of Public Health, Health, Aarhus University
Rare mutations in the gene HNF4A, encoding the transcription factor hepatocyte nuclear factor 4a (HNF-4A), account for ~5% of cases of MODY and more frequent variants in this gene may be involved in multifactorial forms of diabetes. Two low-frequency, non-synonymous variants in HNF4A (V255M, minor allele frequency [MAF] ~0.1%; T130I, MAF ~3.0%)-known to influence downstream HNF-4A target gene expression-are of interest, but previous type 2 diabetes association reports were inconclusive. We aimed to evaluate the contribution of these variants to type 2 diabetes susceptibility through large-scale association analysis.