The role of the HNF4α enhancer in type 2 diabetes variants of the HNF4α enhancer are not a common cause of susceptibility to type 2 diabetes

The genetic causes of type 2 diabetes are not well understood. The disease has been linked to chromosome 20q12-q13.1 a region which harbors the transcription factor HNF4α. Mutations in the coding region of HNF4α cause maturity onset diabetes of the young, an autosomal dominant form of diabetes, but do not account for the linkage to this region. An enhancer element has recently been characterized 6 kb 5′ of the HNF4α P1 promoter containing binding sites for the transcription factors HNF1, HNF4, HNF3, and C/EBP, which are overlapped by glucocorticoid consensus sites. We hypothesized that variation in the enhancer element disrupts HNF4α expression in the liver and increases susceptibility to type 2 diabetes. We screened for variants of the enhancer element in 39 white UK young onset diabetic subjects, giving > 95% power to identify variants with minor allele frequencies of > 5%. No variants of the enhancer element were found in this population. We conclude that variation in the HNF4α enhancer element is not a common cause of susceptibility to type 2 diabetes. © 2002 Elsevier Science (USA). All rights reserved.