褪黑素受体基因多态性与多囊卵巢综合征的相关性：系统评价和荟萃分析。
Association between melatonin receptor gene polymorphisms and polycystic ovarian syndrome: a systematic review and meta-analysis.
机构信息
Center for Reproductive Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
出版信息
Biosci Rep. 2020 Jun 26;40(6). doi: 10.1042/BSR20200824.
BACKGROUND
Polycystic ovarian syndrome (PCOS) is a kind of common gynecological endocrine disorder. And the mutations of melatonin receptor (MTNR) genes are related to the occurrence of PCOS. But previous researches have shown opposite results. So, the object of our systematic review and meta-analysis is to investigate the relationship between MTNR 1A/B polymorphisms and PCOS.
METHODS
PubMed, Embase, Ovid, the Cochrane Library, Web of Science and three Chinese databases (VIP, CNKI and Wanfang) were used to retrieve eligible articles published between January 1980 and February 2020. And we used the odds ratio (OR) and its 95% confidence interval (CI) to investigate the strength of the association by six genetic models, allelic, codominant (homozygous and heterozygous), dominant, recessive and superdominant models. Review Manager 5.3, IBM SPSS statistics 25 and Stata MP 16.0 software were used to do this meta-analysis.
RESULTS
Our meta-analysis involved 2553 PCOS patients and 3152 controls, for two single nucleotide polymorphisms (rs10830963 C> G in MTNR1B and rs2119882 T> C in MTNR1A) and significant associations were found in some genetic models of these single nucleotide polymorphisms (SNPs). For rs10830963, strongly significant was found in the heterozygote model (GC vs. CC, P=0.02). Additionally, a slight trend was detected in the allelic (G vs. C), homozygote (GG vs. CC) and dominant (GG+GC vs. CC) model of rs10830963 (P=0.05). And after further sensitivity analysis, a study with high heterogeneity was removed. In the allelic (P=0.000), homozygote (P=0.001), dominant (P=0.000) and recessive (GG vs. GC+CC, P=0.001) model, strong associations between rs10830963 and PCOS were found. Moreover, for rs2119882, five genetic models, allelic (C vs. T, P=0.000), codominant (the homozygote (CC vs. TT, P=0.000) and heterozygote model (CT vs. TT, P=0.02), dominant (CC + CT vs. TT, P=0.03) and recessive model (CC vs. CT + TT, P=0.000) showed significant statistical associations with PCOS.
CONCLUSION
MTNR1B rs10830963 and MTNR1B rs2119882 polymorphisms are associated with PCOS risk. However, the above conclusions still require being confirmed by much larger multi-ethnic studies.
背景
多囊卵巢综合征（PCOS）是一种常见的妇科内分泌疾病。褪黑素受体（MTNR）基因的突变与 PCOS 的发生有关。但是，之前的研究结果并不一致。因此，我们进行了系统评价和荟萃分析，旨在探讨 MTNR1A/B 多态性与 PCOS 之间的关系。
方法
我们检索了 1980 年 1 月至 2020 年 2 月期间发表的符合条件的文章，使用了 PubMed、Embase、Ovid、Cochrane 图书馆、Web of Science 和三个中文数据库（VIP、CNKI 和万方）。我们使用比值比（OR）及其 95%置信区间（CI），通过 6 种遗传模型（等位、共显性（纯合子和杂合子）、显性、隐性和超显性模型）来评估关联的强度。使用 Review Manager 5.3、IBM SPSS statistics 25 和 Stata MP 16.0 软件进行荟萃分析。
结果
我们的荟萃分析共纳入 2553 名 PCOS 患者和 3152 名对照，涉及两个单核苷酸多态性（MTNR1B 的 rs10830963 C> G 和 MTNR1A 的 rs2119882 T> C），这些单核苷酸多态性的一些遗传模型中发现了显著的关联。对于 rs10830963，在杂合子模型（GC 与 CC，P=0.02）中发现了强烈的关联。此外，在 rs10830963 的等位（G 与 C）、纯合子（GG 与 CC）和显性（GG+GC 与 CC）模型中，存在轻微的趋势（P=0.05）。进一步的敏感性分析显示，在等位（P=0.000）、纯合子（P=0.001）、显性（P=0.000）和隐性（GG 与 GC+CC，P=0.001）模型中，rs10830963 与 PCOS 之间存在强烈的关联。此外，对于 rs2119882，在 5 种遗传模型（等位（C 与 T，P=0.000）、共显性（纯合子（CC 与 TT，P=0.000）和杂合子模型（CT 与 TT，P=0.02）、显性（CC+CT 与 TT，P=0.03）和隐性模型（CC 与 CT+TT，P=0.000）中，发现与 PCOS 有显著的统计学关联。
结论
MTNR1B rs10830963 和 MTNR1B rs2119882 多态性与 PCOS 风险相关。然而，上述结论仍需要通过更大的多民族研究来证实。
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