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OBJECTIVE-Hepatocyte nuclear factor 1β (HNF1β) is a transcription factor that is critical for pancreatic cell formation and glucose homeostasis. Previous studies have reported that common variants of HNF1β were associated with type 2 diabetes in Caucasians and West Africans. However, analysis in the subjects from the Botnia study and Malmö Preventive Project produced conflicting results, and the role for HNF1β in type 2 diabetes susceptibility remains unclear. We therefore investigated common variants across the HNF1β gene in a Chinese population.
RESEARCH DESIGN AND METHODS-Fifteen tagging single nucleotide polymorphisms (SNPs) were analyzed for association with type 2 diabetes in subjects with type 2 diabetes (n = 1,859) and normal glucose regulation (n = 1,785).
RESULTS-Consistent with the initial study, we observed evidence that the risk G allele of rs4430796 in intron 2 was significantly associated with type 2 diabetes (odds ratio 1, 16 [95% CI 1.05-1.29], P = 0.0035, empirical P = 0.0475). Furthermore, the at-risk G allele was associated with earlier age at diagnosis in the type 2 diabetic subjects (P = 0.0228).
CONCLUSIONS-The result of this study provides evidence that variants in the HNFl β region contribute to susceptibility to type 2 diabetes in the Chinese population. Diabetes 58:1023-1027, 2009
Hepatocyte nuclear factor 1β (HNFl β, also known as transcription factor [TCFJ2), is a homeodomain-containing transcription factor that functions as a homodimer or heterodimer with its homologous partner HNFIa (1). HNFl β is widely expressed in a number of tissues where it takes a vital role in embryonic development and pancreatic cell formation and is involved in the β-cell transcription factor network (2,3). Heterozygous mutation of the HNFl β gene was identified in an autosomal dominant, early-onset subtype of diabetes known as maturity-onset diabetes of the young type 5 (MODY5) in Caucasian, Japanese, and Chinese populations (4-6). It is well recognized that common variants of genes that cause monogenic forms of diabetes may also have a role in common type 2 diabetes susceptibility, such as P12A polymorphism in PPARG, E23K polymorphism in KCNJIl, and common variants in the promoter region of HNF4A (7-9). Recently, single nucleotide polymorphisms (SNPs) on HNFl β were identified to be associated with type 2 diabetes in Finland, Sweden, and Canada populations (10,11). The association signals, which were separated...