OBJECTIVE: Recent publications have found an association between common variants near the hepatocyte nuclear factor 4 alpha (HNF4A) P2 promoter and type 2 diabetes in some populations but not in others, and the role for HNF4A in type 2 diabetes has remained unclear. In an attempt to address these inconsistencies, we investigated HNF4A single nucleotide polymorphisms (SNPs) in a large population-based sample and included a meta-analysis of published studies. RESEARCH DESIGN AND METHODS: We genotyped 12 SNPs in the HNF4A region in a Norwegian population-based sample of 1,644 individuals with type 2 diabetes and 1,879 control subjects (the Nord-Trøndelag Health Study [HUNT] 2). We combined our data with all previously published case/control studies and performed a meta-analysis. RESULTS: Consistent with initial studies, we found a trend toward association for the SNPs rs1884613 (odds ratio [OR] 1.17 [95% CI 1.03-1.35]) and rs2144908 (1.21 [1.05-1.38]) in the P2 region and for rs4812831 (1.21 [1.02-1.44]), located 34 kb downstream of the P2 promoter. Meta-analysis, comprising 12,292 type 2 diabetic case and 15,519 control subjects, revealed a nonsignificant OR of 1.05 (95% CI 0.98-1.12) but with significant heterogeneity between the populations. We therefore performed a subanalysis including only the data for subjects from Scandinavia. Among the 4,000 case and 7,571 control Scandinavian subjects, a pooled OR of 1.14 (1.06-1.23), P = 0.0004, was found for the SNP rs1884613. CONCLUSIONS: Our results suggest that variation in the HNF4A region is associated with type 2 diabetes in Scandinavians, highlighting the importance of exploring small genetic effects in large, homogenous populations.
OBJECTIVE: Recent publications have found an association between common variants near the hepatocyte nuclear factor 4 alpha (HNF4A) P2 promoter and type 2 diabetes in some populations but not in others, and the role for HNF4A in type 2 diabetes has remained unclear. In an attempt to address these inconsistencies, we investigated HNF4A single nucleotide polymorphisms (SNPs) in a large population-based sample and included a meta-analysis of published studies. RESEARCH DESIGN AND METHODS: We genotyped 12 SNPs in the HNF4A region in a Norwegian population-based sample of 1,644 individuals with type 2 diabetes and 1,879 control subjects (the Nord-Trøndelag Health Study [HUNT] 2). We combined our data with all previously published case/control studies and performed a meta-analysis. RESULTS: Consistent with initial studies, we found a trend toward association for the SNPs rs1884613 (odds ratio [OR] 1.17 [95% CI 1.03-1.35]) and rs2144908 (1.21 [1.05-1.38]) in the P2 region and for rs4812831 (1.21 [1.02-1.44]), located 34 kb downstream of the P2 promoter. Meta-analysis, comprising 12,292 type 2 diabetic case and 15,519 control subjects, revealed a nonsignificant OR of 1.05 (95% CI 0.98-1.12) but with significant heterogeneity between the populations. We therefore performed a subanalysis including only the data for subjects from Scandinavia. Among the 4,000 case and 7,571 control Scandinavian subjects, a pooled OR of 1.14 (1.06-1.23), P = 0.0004, was found for the SNP rs1884613. CONCLUSIONS: Our results suggest that variation in the HNF4A region is associated with type 2 diabetes in Scandinavians, highlighting the importance of exploring small genetic effects in large, homogenous populations.
Authors: P Ungaro; R Teperino; P Mirra; M Longo; M Ciccarelli; G A Raciti; C Nigro; C Miele; P Formisano; F Beguinot Journal: Diabetologia Date: 2010-04-16 Impact factor: 10.122
Authors: J K Hertel; S Johansson; H Raeder; K Midthjell; V Lyssenko; L Groop; A Molven; P R Njølstad Journal: Diabetologia Date: 2008-04-24 Impact factor: 10.122
Authors: Yoon Shin Cho; Chien-Hsiun Chen; Cheng Hu; Jirong Long; Rick Twee Hee Ong; Xueling Sim; Fumihiko Takeuchi; Ying Wu; Min Jin Go; Toshimasa Yamauchi; Yi-Cheng Chang; Soo Heon Kwak; Ronald C W Ma; Ken Yamamoto; Linda S Adair; Tin Aung; Qiuyin Cai; Li-Ching Chang; Yuan-Tsong Chen; Yutang Gao; Frank B Hu; Hyung-Lae Kim; Sangsoo Kim; Young Jin Kim; Jeannette Jen-Mai Lee; Nanette R Lee; Yun Li; Jian Jun Liu; Wei Lu; Jiro Nakamura; Eitaro Nakashima; Daniel Peng-Keat Ng; Wan Ting Tay; Fuu-Jen Tsai; Tien Yin Wong; Mitsuhiro Yokota; Wei Zheng; Rong Zhang; Congrong Wang; Wing Yee So; Keizo Ohnaka; Hiroshi Ikegami; Kazuo Hara; Young Min Cho; Nam H Cho; Tien-Jyun Chang; Yuqian Bao; Åsa K Hedman; Andrew P Morris; Mark I McCarthy; Ryoichi Takayanagi; Kyong Soo Park; Weiping Jia; Lee-Ming Chuang; Juliana C N Chan; Shiro Maeda; Takashi Kadowaki; Jong-Young Lee; Jer-Yuarn Wu; Yik Ying Teo; E Shyong Tai; Xiao Ou Shu; Karen L Mohlke; Norihiro Kato; Bok-Ghee Han; Mark Seielstad Journal: Nat Genet Date: 2011-12-11 Impact factor: 38.330
Authors: Jens K Hertel; Stefan Johansson; Helge Ræder; Carl G P Platou; Kristian Midthjell; Kristian Hveem; Anders Molven; Pål R Njølstad Journal: BMC Med Genet Date: 2011-02-04 Impact factor: 2.103
Authors: Rong Chen; Alex A Morgan; Joel Dudley; Tarangini Deshpande; Li Li; Keiichi Kodama; Annie P Chiang; Atul J Butte Journal: Genome Biol Date: 2008-12-05 Impact factor: 13.583