雌激素受体α基因多态性与女童1型糖尿病易感性的相关性研究

Association of estrogen receptor gene polymorphisms with type 1 diabetes mellitus in children

目的本研究旨在探讨雌激素受体-α(estrogen receptor-α,ESR1)基因PvuⅡ(rs2234693,C>T)和XbaⅠ(rs9340799,A>G)位点多态性与女童1型糖尿病(type 1 diabetes,T1D)易感性的相关性。方法纳入2016年1月至2019年12月于重庆三峡中心医院就诊的86例新发T1D女性患儿作为研究对象,并选择同期于本院参加健康体检的100例健康女童作为健康对照。测定研究对象的身高、体重和相关代谢指标;采用毛细管电泳和片段分析(SNaPshot)技术对ESR1基因进行分型;采用实时荧光定量聚合酶链式反应(RT-PCR)法检测ESR1基因的mRNA表达量。结果基因分型结果显示T1D组和对照组的PvuII位点基因型分布差异有统计学意义(χ^2=11.672,P=0.003),而XbaI位点基因型分布差异无统计学意义(χ^2=5.433,P=0.066),T1D组的PvuII位点T等位基因频率和XbaI位点G等位基因频率均显著高于对照组(PvuII T vs C:OR=1.909,95%CI=1.261~2.892,P=0.002;XbaI G vs A:OR=1.815,95%CI=1.112~2.961,P=0.016)。携带PvuII T等位基因的T1D患者糖化血红蛋白(HbA1c)和总胆固醇(total cholesterol,TC)水平显著高于携带CC基因型的患者(P均<0.05),携带XbaI G等位基因的T1D患者低密度脂蛋白(LDL-C)和TC水平显著高于携带AA基因型的患者(P均<0.05)。T1D患者的ESR1基因mRNA相对表达量显著低于对照组(0.42±0.05 vs 1.04±0.16,t=6.227,P<0.001)。PvuII位点CC、CT和TT基因型的T1D患者ESR1基因mRNA相对表达量差异有统计学意义(F=5.823,P<0.001),XbaI位点AA、AG和GG基因型的T1D患者ESR1基因mRNA相对表达量差异也有统计学意义(F=5.415,P<0.001)。结论ESR1基因PvuII和XbaI位点多态性可通过影响基因表达,参与到女童T1D的发生、发展中。

Objective To investigate the relationships of estrogen receptor-α(ESR1)gene PvuⅡ(rs2234693,C>T)and XbaⅠ(rs9340799,A>G)polymorphisms and susceptibility of type 1 diabetes for female children(T1D).Methods From Jan.2016 to Dec.2019,86 female children with newly diagnosed T1D who were admitted to Chongqing Three Gorges Central hospital were selected as the study subjects,and 100 healthy children who underwent physical examination in our hospital during the same period were selected as the healthy control.The height,weight and related metabolic indexes of the subjects were measured.The ESR1 gene was genotyped by capillary electrophoresis and SNaPshot.The mRNA expression of ESR1 gene was detected by real-time fluorescence quantitative polymerase chain reaction(RT-PCR).Results Genotyping results showed that PvuII genotype distribution between T1D group and the control group was statistically significant(χ^2=11.672,P=0.003),but XbaI genotype distribution between T1D patients and controls had no significant difference(χ^2=5.433,P=0.066).PvuII locus T allele frequency and XbaI locus G allele frequency were significantly in T1D group higher than in the control group(PvuII T vs C:OR=1.909,95%CI=1.261-2.892,P=0.002;XbaI G vs A:OR=1.815,95%CI=1.112-2.961,P=0.016).Glycated hemoglobin(HbA1c)and total cholesterol(TC)levels in T1D patients with PvuII T allele were significantly higher than those with CC genotype(all P<0.05).Low-density lipoproteins(LDL-C)and total cholesterol(TC)levels in T1D patients with XbaI G allele were significantly higher than those with AA genotypes(both P<0.05).The relative expression of ESR1 gene mRNA in T1D patients was significantly lower than that in the control group(0.42±0.05 vs 1.04±0.16,t=6.227,P<0.001).The relative expression of ESR1 gene mRNA in T1D patients with PvuII CC,CT and TT genotypes was statistically different(F=5.823,P<0.001),and the relative ESR1 gene mRNA in T1D patients with XbaI AA,AG and GG genotypes was also statistically different(F=5.415,P<0.001).Conclusion PvuII and XbaI olymorphismsof ESR1 genes may be involved in the occurrence and development of T1D in female children by influencing gene expression.