Diabet. Med. 27, 1443–1449 (2010)AbstractAims  POU class 2 homeobox 1 (POU2F1), also known as octamer‐binding transcription factor‐1 (OCT‐1), is a ubiquitous transcription factor that plays a key role in the regulation of genes related to inflammation and cell cycles. POU2F1 is located on chromosome 1q24, a region with linkage for Type 2 diabetes in Chinese and other populations. We examined the association of POU2F1 genetic variants with Type 2 diabetes in Hong Kong Chinese using two independent cohorts.Methods  We genotyped five haplotype‐tagging single nucleotide polymorphisms at POU2F1 in 1378 clinic‐based patients with Type 2 diabetes and 601 control subjects, as well as 707 members from 179 families with diabetes.Results  We found significant associations of rs4657652, rs7532692, rs10918682 and rs3767434 (OR = 1.26–1.59, 0.0003 < Punadjusted < 0.035) with Type 2 diabetes in the clinic‐based case–control cohorts. Rs3767434 was also associated with Type 2 diabetes (OR = 1.55, Punadjusted = 0.013) in the family‐based cohort. Meta‐analysis revealed similar associations. In addition, the risk G allele of rs10918682 showed increased usage of insulin treatment during a mean follow‐up period of 7 years [hazard ratio = 1.50 (1.05–2.14), P = 0.025].Conclusions  Using separate cohorts, we observed consistent results showing the contribution of multiple variants at POU2F1 to the risk of Type 2 diabetes.