Brief Genetics Report Common Variants of the Hepatocyte Nuclear Factor-4 P2 Promoter Are Associated With Type 2 Diabetes in the U.K. Population

Hepatocyte nuclear factor (HNF)-4 is part of a tran-scription factor network that is key for the development and function of the -cell. Rare mutations in the HNF4 gene cause maturity-onset diabetes of the young. A number of type 2 diabetes linkage studies have found evidence of linkage to 20q12–13.1 where the HNF4 gene is located. Two recent studies have found an association between four common variants of the alter-native P2 promoter region and type 2 diabetes. These variants are in strong linkage disequilibrium, and the minor alleles define one common risk haplotype. In both studies, the risk haplotype explained a large proportion of the evidence of linkage to 20q12–13.1. We aimed to assess this haplotype in a U.K. Caucasian study of 5,256 subjects. We typed two single nucleotide polymor