雌激素受体基因多态性与妊娠糖尿病的相关性研究

Correlation between polymorphism of estrogen receptor gene and gestational diabetes mellitus

目的 观察雌激素受体(ER)α和β基因多态性与妊娠糖尿病(GDM)的关系.方法 392例GDM患者(GDM组)和308名糖耐量正常孕妇(对照组)均来自2016年5月至2017年12月在淄博市妇幼保健院糖尿病筛查门诊就诊的孕妇,GDM诊断依据参照2014年中华医学会妇产科学分会产科学组与中华医学会围产医学分会妊娠合并糖尿病协作组制订的诊断标准,采用PCR-限制性片段长度多态性(RFLP)方法对ERα和β基因(Xba Ⅰ、PvuⅡ、Rsa Ⅰ、Alu Ⅰ酶切位点)多态性进行检测,并采用SHEsis在线计算平台进行单体型分析.结果 两组间ERα Xba Ⅰ和PvuⅡ酶切位点以及ERβRsa Ⅰ酶切位点的基因型及等位基因分布频率差异均无统计学意义(P =0.870、0.287、0.904、0.982、0.725、0.720);而ERβ Alu Ⅰ酶切位点的基因型及等位基因分布频率差异存在统计学意义(P =0.007、0.003),携带有a等位基因的个体发生GDM的风险是A的1.559倍(95% CI:1.161~2.095,P=0.003).GDM组R-a单体型所占频率显著高于对照组(OR=1.562,95% CI:1.162~2.099,P=0.003).结论 GDM的遗传易感性与ERα基因多态性无关,而与ERβ基因多态性存在关联性,R、a等位基因可能是其易感等位基因.

Objective To investigate the relationship between genetic polymorphisms of estrogen receptor (ER)α,β and gestational diabetes mellitus (GDM).Methods A total of 392 patients with GDM (GDM group) and 308 pregnant women with normal glucose tolerance (control group) who underwent diabetes screening were included in this study in the clinic of the Maternal and Child Health Care Hospital of Zibo from May 2016 to December 2017.The diagnosis of GDM was based on the 2014 diagnostic criteria of the Department of Obstetrics and Gynecology and the Department of Perinatal Medicine of the Chinese Medical Association.Polymorphisms of ERα and ERβ genes (Xba Ⅰ,Pvu Ⅱ,Rsa Ⅰ,Alu Ⅰ) were examined by polymerase chain reaction-based restriction fragment length polymorphism (RFLP) and the haplotype analysistwas conducted by SHEsis on-line computing platform.Results There was no significant difference in the distribution frequency of genotype and allele in enzyme sites of Xba Ⅰ,Pvu Ⅱ and Rsa Ⅰ between these two groups(P =0.870,0.287,0.904,0.982,0.725,0.720).In enzyme sites of Alu Ⅰ,there was significant difference in the distribution frequency of genotype and allele between these two groups (P = 0.007,0.003).The risk of GDM in persons with a allele was 1.559-fold compared with persons with A allele (95% CI:1.161-2.095,P = 0.003).The frequency of R-a haplotype was significantly higher in GDM group than that in control group(OR=1.562,95%CI:1.162-2.099,P=0.003).Conclusion The polymorphism of ERβ gene but not ERα gene is associated with the susceptibility of GDM,and the R,a allele may be the susceptible alleles.