17β羟基类固醇脱氢酶5型和6型基因多态性与多囊卵巢综合征发病风险相关性的Meta分析

目的 系统评价17β-羟基类固醇脱氢酶5型（17beta-hydroxysteroid dehydrogenase type 5，HSD17B5）和6型（17beta-hydroxysteroid dehydrogenase type 6，HSD17B6）单核苷酸基因多态性（single nucleotide polymorphisms，SNP）与多囊卵巢综合征（polycystic ovary syndrome，PCOS）发病风险的关联性。方法 计算机检索PubMed、The Cochrane Library、EMBASE （OVID）、CNKI、CBM、万方和维普数据库，搜索国内外公开发表的有关HSD17B5或HSD17B6基因多态性与PCOS相关性的研究报告，检索时间均为建库至2017年6月30日。两名评价者严格按照纳入与排除标准独立筛选文献、提取资料及评估纳入研究的偏倚风险后，采用Rev Man 5.3软件进行分析Meta分析。结果 共纳入8篇病例对照研究文献，5篇文献涉及HSD17B5 rs3763676 SNP与PCOS发病风险相关性的研究，共包括病例组899例和对照组751例其中2篇因研究人群中的G突变基因为稀有基因无法进行HWE检验及统计学分析而只进行了定性描述性分析，3篇进行遗传模型Meta分析结果显示：rs3763676基因多态性与PCOS易感性的关联性无统计学意义（G vs A：OR=1.21，95% CI：0.98~1.49，P=0.070；GG+AG vs AA：OR=1.26，95% CI：0.85~1.86，P=0.250；GG vs AG+AA：OR=1.35，95% CI：0.86~2.12，P=0.190；GG vs AA：OR=1.47，95% CI：0.91~2.38，P=0.110；AG vs AA：OR=1.19，95% CI：0.79~1.78，P=0.410）。4篇文献关于HSD17B6 rs898611 SNP，共包括病例组1 065例和对照组942例，遗传模型Meta分析结果显示：除共显性模型C vs T差异有统计学意义外（C vs T：OR=1.46，95% CI：1.02~2.09，P=0.040），其余差异均无统计学意义（C vs T：OR=1.13，95% CI：0.96~1.32，P=0.140；CC+CT vs TT：OR=1.06，95% CI：0.88~1.27，P=0.570；CC vs CT+TT：OR=1.48，95% CI：0.95~2.29，P=0.080；CT vs TT：OR=0.99，95% CI：0.81~1.21，P=0.950）。结论 HSD17B5 rs3763676和HSD17B6 rs898611单核苷酸基因多态性与PCOS的发病尚不能提示存在相关性。

Association between the polymorphisms of 17beta-hydroxysteroid dehydrogenase type 5 or 6 and the risk of polycystic ovary syndrome: a systemic review and meta analysis

Objective To systematically evaluate the association between 17beta-hydroxysteroid dehydrogenase type 5 (HSD17B5) and type 6 (HSD17B6) single nucleotide polymorphisms (SNP) and the risk of polycystic ovary syndrome (PCOS).Methods A comprehensive electronic search about published reports on the association of HSD17B5 or HSD17B6 gene polymorphisms with PCOS in China and abroad,which was conducted in PubMed. The Cochrane Library, EMBASE (OVID), CNIK, CBM, WangFang Date and VIP database and the retrieval time was up to June 2017. Two reviewers independently screened the literature according to inclusion and exclusion criteria, extracted data and assessed the bias risk of the included studies. The pooled ORs were performed using the Revman 5.3 software.Results Eight case-control studies were included:5 were about HSD17B5 rs3763676 that including 899 cases and 751 controls and 4 were about HSD17B6 rs3763676 that including 1 065 cases and 942 controls. The results of genetic model meta analysis in 3 studies showed no significant association between HSD17B5 rs3763676 gene polymorphisms and risks of PCOS(G vs A:OR=1.21,95% CI:0.98-1.49,P=0.070;GG+AG vs AA:OR=1.26,95% CI:0.85-1.86,P=0.250;GG vs AG+AA:OR=1.35,95% CI:0.86-2.12,P=0.190;GG vs AA:OR=1.47,95% CI:0.91-2.38,P=0.110;AG vs AA:OR=1.19,95% CI:0.79-1.78,P=0.410). Approximately, no significant association between HSD17B6 rs3763676 gene polymorphisms and risks of PCOS (C vs T:OR=1.13,95% CI:0.96-1.32,P=0.140;CC+CT vs TT:OR=1.06,95% CI:0.88-1.27,P=0.570;CC vs CT+TT:OR=1.48,95% CI:0.95-2.29,P=0.080;CT vs TT:OR=0.99,95% CI:0.81-1.21,P=0.950) except for CC vs TT codominant model(CC vs TT:OR=1.46,95% CI:1.02-2.09,P=0.040), but the results should be interpreted with caution.Conclusion Both HSD17B5 rs3763676 and HSD17B6 rs898611 single nucleotide polymorphisms are no associated with the risks of PCOS, but the results should be interpreted with caution.