Molecular Genetics and Biology of Complex Diseases Department, Institute of Medical Research A. Lanari, University of Buenos Aires--National Council of Scientific and Technological Research, Combatientes de Malvinas 3150, Buenos Aires (1427), Argentina.
Mol Genet Metab. 2010 Jan;99(1):80-9. doi: 10.1016/j.ymgme.2009.08.004.
The nuclear receptor hepatocyte nuclear factor 4alpha (HNF4alpha) contributes to the regulation of a large fraction of liver and pancreatic islet transcriptomes.
To evaluate the influence of HNF4alpha polymorphisms across the entire locus on the occurrence of type 2 diabetes (T2D) by means of a meta-analysis.
We evaluated haplotype block structure of HNF4alpha variants owing to linkage disequilibrium (LD). From 1455 reports, we evaluated 21 observational studies.
Six haplotype blocks of LD were constructed with SNPs with r(2)>0.8; there were also 14 unlinked SNPs. Overall, we included 22,920 cases and 26.657 controls. Among 17 heterogeneous studies (21,881 cases and 24,915 controls), including 3 SNPs of P2 promoter region in block 1, we observed a significant association with T2D in fixed (OR 0.94, 95%CI: 0.905-0.975, p=0.001) and random (OR 0.988, 95%CI: 0.880-0.948, p=0.000012) model. Three homogeneous studies were evaluated in block 2 (2684 cases and 2059 controls), and a significant association with T2D was also observed: OR: 1.121, 95%CI 1.013-1.241, p=0.027. Three additional variants were associated with T2D: two intronic SNPs (rs4810424: OR: 1.080, 95%CI: 1.010-1.154, p<0.03 and rs3212183: OR: 0.843, 95%CI: 0.774-0.918, p<0.00009) and one missense variant (rs1800961: OR: 0.770, 95%CI: 0.595-0.995, p<0.05, 6562 cases and 6723 controls).
In addition to HNF4alpha variants in the promoter region, other SNPs may be involved on the occurrence of T2D.
核受体肝细胞核因子 4α（HNF4α）有助于调节大量肝脏和胰岛转录本。
通过荟萃分析评估整个基因座上的 HNF4α 多态性对 2 型糖尿病（T2D）发生的影响。
我们评估了由于连锁不平衡（LD）而导致 HNF4α 变体的单倍型块结构。从 1455 份报告中，我们评估了 21 项观察性研究。
构建了 6 个具有 LD 的单倍型块，其中包含 r（2）>0.8 的 SNP；还有 14 个不相关的 SNP。总共纳入了 22920 例病例和 26657 例对照。在 17 项异质性研究（21881 例病例和 24915 例对照）中，包括 1 号块 P2 启动子区域的 3 个 SNP，我们观察到与 T2D 存在显著关联，固定模型（OR 0.94，95%CI：0.905-0.975，p=0.001）和随机模型（OR 0.988，95%CI：0.880-0.948，p=0.000012）。在 2 号块中评估了 3 项同质研究（2684 例病例和 2059 例对照），也观察到与 T2D 的显著关联：OR：1.121，95%CI 1.013-1.241，p=0.027。另外 3 个变体与 T2D 相关：2 个内含子 SNP（rs4810424：OR：1.080，95%CI：1.010-1.154，p<0.03 和 rs3212183：OR：0.843，95%CI：0.774-0.918，p<0.00009）和 1 个错义变体（rs1800961：OR：0.770，95%CI：0.595-0.995，p<0.05，6562 例病例和 6723 例对照）。
除了启动子区域的 HNF4α 变体之外，其他 SNP 也可能与 T2D 的发生有关。
