Bioinformatics Laboratory, Department of Statistics, University of Rajshahi, Rajshahi, Bangladesh.
Department of Genetic Engineering and Biotechnology, University of Dhaka, Dhaka, Bangladesh.
PLoS One. 2022 Aug 16;17(8):e0273042. doi: 10.1371/journal.pone.0273042. eCollection 2022.
HIF1A gene polymorphisms have been confirmed the association with cancer risk through the statistical meta-analysis based on single genetic association (SGA) studies. A good number SGA studies also investigated the association of HIF1A gene with several other diseases, but no researcher yet performed statistical meta-analysis to confirm this association more accurately. Therefore, in this paper, we performed a statistical meta-analysis to draw a consensus decision about the association of HIF1A gene polymorphisms with several diseases except cancers giving the weight on large sample size. This meta-analysis was performed based on 41 SGA study's findings, where the polymorphisms rs11549465 (1772 C/T) and rs11549467 (1790 G/A) of HIF1A gene were analyzed based on 11544 and 7426 cases and 11494 and 7063 control samples, respectively. Our results showed that the 1772 C/T polymorphism is not significantly associated with overall disease risks. The 1790 G/A polymorphism was significantly associated with overall diseases under recessive model (AA vs. AG + GG), which indicates that the A allele is responsible for overall diseases though it is recessive. The subgroup analysis based on ethnicity showed the significant association of 1772 C/T polymorphism with overall disease for Caucasian population under the all genetic models, which indicates that the C allele controls overall diseases. The ethnicity subgroup showed the significant association of 1790 G/A polymorphism with overall disease for Asian population under the recessive model (AA vs. AG + GG), which indicates that the A allele is responsible for overall diseases. The subgroup analysis based on disease types showed that 1772 C/T is significantly associated with chronic obstructive pulmonary disease (COPD) under two genetic models (C vs. T and CC vs. CT + TT), skin disease under two genetic models (CC vs. TT and CC + CT vs. TT), and diabetic complications under three genetic models (C vs. T, CT vs. TT and CC + CT vs. TT), where C allele is high risk factor for skin disease and diabetic complications (since, ORs > 1), but low risk factor for COPD (since, ORs < 1). Also the 1790 G/A variant significantly associated with the subgroup of cardiovascular disease (CVD) under homozygote model, diabetic complications under allelic and homozygote models, and other disease under four genetic models, where the A is high risk factor for diabetic complications and low risk factor for CVD. Thus, this study provided more evidence that the HIF1A gene is significantly associated with COPD, CVD, skin disease and diabetic complications. These might be the severe comorbidities and risk factors for multiple cancers due to the effect of HIF1A gene and need further investigations accumulating large number of studies.
HIF1A 基因多态性已通过基于单核苷酸基因关联 (SGA) 研究的统计荟萃分析得到证实与癌症风险相关。许多 SGA 研究还调查了 HIF1A 基因与其他几种疾病的关联，但尚无研究人员进行统计荟萃分析以更准确地确认这种关联。因此，在本文中，我们基于 41 项 SGA 研究的结果进行了统计荟萃分析，根据 11544 例和 7426 例病例和 11494 例和 7063 例对照样本，对 HIF1A 基因多态性与癌症以外的几种疾病的关联进行了分析。rs11549465（1772C/T）和 rs11549467（1790G/A）的多态性。我们的结果表明，1772C/T 多态性与总体疾病风险无显著相关性。1790G/A 多态性在隐性模型下与总体疾病显著相关（AA vs. AG + GG），这表明 A 等位基因虽然是隐性的，但与总体疾病有关。基于种族的亚组分析表明，在所有遗传模型下，1772C/T 多态性与高加索人群的总体疾病显著相关，这表明 C 等位基因控制着总体疾病。基于疾病类型的亚组分析表明，1790G/A 多态性在亚洲人群的隐性模型下与总体疾病显著相关（AA vs. AG + GG），这表明 A 等位基因与总体疾病有关。基于种族的亚组分析表明，1772C/T 多态性与慢性阻塞性肺疾病（COPD）在两种遗传模型（C vs. T 和 CC vs. CT + TT）下显著相关，在两种遗传模型（CC vs. TT 和 CC + CT vs. TT）下与皮肤病显著相关，在三种遗传模型（C vs. T、CT vs. TT 和 CC + CT vs. TT）下与糖尿病并发症显著相关，其中 C 等位基因是皮肤病和糖尿病并发症的高风险因素（因为 ORs>1），但 COPD 的低风险因素（因为 ORs<1）。此外，1790G/A 变体在同型合子模型下与心血管疾病（CVD）亚组显著相关，在等位基因和同型合子模型下与糖尿病并发症显著相关，在四种遗传模型下与其他疾病显著相关，其中 A 是糖尿病并发症的高风险因素，是 CVD 的低风险因素。因此，本研究提供了更多证据表明 HIF1A 基因与 COPD、CVD、皮肤病和糖尿病并发症显著相关。由于 HIF1A 基因的作用，这些可能是多种癌症的严重合并症和危险因素，需要进一步研究积累大量研究。
