Studies in 3,523 Norwegians and meta-analysis in 11,571 subjects indicate that variants in the hepatocyte nuclear factor 4α (HNF4A) P2 region are associated with type 2 diabetes in Scandinavians
Studies in 3,523 Norwegians and meta-analysis in 11,571 subjects indicate that variants in the hepatocyte nuclear factor 4α (HNF4A) P2 region are associated with type 2 diabetes in Scandinavians
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DOI：
10.2337/db07-0513
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发表时间：
2007-12-01
期刊：
影响因子：
7.7
通讯作者：
Njolstad, Pal Rasmus
中科院分区：
文献类型：
--
作者：
Johansson, Stefan;Raeder, Helge;Njolstad, Pal Rasmus
最近的出版物发现，在某些人群中，肝细胞核因子4 α（HNF 4A）P2启动子附近的常见变异与2型糖尿病之间存在关联，但在其他人群中则没有，HNF 4A在2型糖尿病中的作用仍不清楚。为了解决这些不一致性，我们在一个大的基于人群的样本中调查了HNF 4A单核苷酸多态性（SNP），并对已发表的研究进行了荟萃分析。研究设计和方法-我们在挪威基于人群的样本中对HNF 4A区域的12个SNP进行了基因分型，该样本包括1，644名患有2型糖尿病的个体和1名患有2型糖尿病的个体，879名对照受试者（Nord-Trondelag健康研究[HUNT] 2）。我们将我们的数据与所有先前发表的病例/对照研究相结合，并进行了荟萃分析。我们发现SNPs rs 1884613（比值比[OR] 1.17 [95%CI 1.03-1.35]）和rs 2144908（1.21 [1.05-1.38]）以及位于P2启动子下游34 kb的rs 4812831（1.21 [1.02-1.44]）。荟萃分析包括12，292例2型糖尿病病例和15，519例对照受试者，显示OR为1.05（95%CI 0.98-1.12），但人群之间存在显著异质性。因此，我们进行了亚组分析，仅包括来自斯堪的纳维亚的受试者的数据。在4，000例病例和7，571例对照斯堪的纳维亚受试者中，SNP rs 1884613的合并OR为1.14（1.06-1.23），P = 0.0004。结论-我们的研究结果表明，HNF 4A区域的变异与斯堪的纳维亚人的2型糖尿病相关，突出了在大型同质人群中探索小遗传效应的重要性。
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-Trondelag 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.