糖尿病性骨质疏松患者雌激素受体α基因XbaI(rs9340799)SNP和HbA1c水平交互作用与疾病易感性分析  

Analysis of Interaction between Estrogen ReceptorαGene XbaI(rs9340799)SNP and HbA1c Level and Disease Susceptibility in Patients with Diabetes Osteoporosis

作　　者：汤小峰[1] 蒋艺兰 朱蓓[1] TANG Xiao-feng;JIANG Yi-lan;ZHU Bei(Department of Endocrinology,Rugao People’s Hospital,Jiangsu Nantong 226500,China)

机构地区：[1]如皋市人民医院内分泌科,江苏南通226500

出　　处：《现代检验医学杂志》2023年第1期38-43,共6页Journal of Modern Laboratory Medicine

摘　　要：目的探讨糖尿病性骨质疏松症(diabetic osteoporosis,DO)患者雌激素受体α(estrogen receptorα,ERα)基因XbaI(rs9340799)单核苷酸多态性(single nucleotide polymorphism,SNP)和糖化血红蛋白(glycosylated hemoglobin A1c,HbA1c)水平交互作用与疾病易感性的关系。方法选择2019年2月~2021年11月于如皋市人民医院就诊的DO患者117例,T2DM患者112例和108例健康体检者(对照组)。采用高效液相层析法(high pressure liquid chromatography,HPLC)测定三组人群的HbA1c水平,并通过双脱氧末端终止法(Sanger法)检测三组人群ERa基因XbaI(rs9340799)SNP。采用多因素Logistic回归模型分析DO发生的危险因素,估算ERa基因XbaI39.32SNP和HbA1c水平与DO发病风险的调整比值比(odds ratio,OR)及95%置信区间(95%confidence interval,95%CI),分析XbaI SNP与HbA1c水平的交互作用。结果对照组、T2DM组和DO组患者HbA1c水平分别为5.07%±0.85%,7.94%±1.32%和9.23%±1.40%,差异有统计学意义(F=26.671,P<0.05)。DO组、T2DM组和对照组AA基因频率(11.11%,33.93%和46.30%)、AG基因频率(49.57%,39.28%和33.33%)、GG基因频率(39.32%,26.79%和20.37%),差异均有统计学意义(χ^(2)=37.174,10.600,14.307,均P<0.05)。DO组、T2DM组和对照组等位基因A基因频率(36.75%,61.61%和74.07%)、等位基因G基因频率(63.25%,38.39%和25.93%)差异均有统计学意义(均χ^(2)=36.305,P<0.001)。Logistic回归分析结果显示,HbA1c水平和ERa基因XbaI(AG/GG)与DO的发生显著相关(P<0.05)。单纯6.5%≤HbA1c<9.0%的OR_(e1)为6.231,单独携带XbaI(AG)型的OR_(g1)为5.384,二者同时存在时交互作用OR_(e1g1)为33.978,交互系数γ=β_(e1g1)/β_(e1)>1,OR_(e1g1)>OR_(e1)×OR_(g1)为超相乘模型。6.5%≤HbA1c<9.0%和XbaI(AG/GG)、HbA1c≥9.0%和XbaI(AG/GG)均存在正向交互作用(均γ>1)。结论携带XbaI(AG)和XbaI(GG)基因型的个体属DO高危人群,这些基因型和HbA1c水平的交互作用促进了DO的发生发展,临床可通过控制HbA1c水平以及基因调控达到预防DO�Objective To investigate the interaction between estrogen receptor alpha(ERa)single nucleotide polymorphism(SNP)and glycosylated hemoglobin A1c(HbA1c)level and the relationship of susceptibility to diabetic osteoporosis(DO).Method A total of 117 patients with DO,112 patients with type 2 diabetes mellitus(T2DM)were selected,and 108 healthy subjects were selected as the control group.The glycated hemoglobin(HbA1c)levels of the three groups was determined by high pressure liquid chromatography(HPLC),and the ERαgene XbaI(rs9340799)SNP was detected by dideoxy terminal termination method.Multivariate Logistic regression model was used to analyze the risk factors for the occurrence of DO,and the adjusted odds ratio(OR)and 95%confidence interval(95%CI)of the levels of ERa gene XbaI SNP and HbA1c and the risk of DO incidence were estimated.Interaction of XbaI SNPs with HbA1c levels.Results The level of HbA1c in control group,T2DM group and DO group were 5.07%±0.85%,7.94%±1.32%and 9.23%±1.40%,respectively,and the difference was statistically significant(F=26.671,P<0.05).The frequencies of AA gene(11.11%,33.93%and 46.30%).AG gene(49.57%,39.28%and 33.33%),and GG gene(39.32%,26.79%,20.37%),in the three groups were statistically significant(χ^(2)=37.174,10.600,14.307,all P<0.05).The distribution of gene A(36.75%,61.61%,74.07%)and gene G(63.25%,38.29%,25.93%),in the three groups were statistically significant(allχ^(2)=36.305,P<0.001).Logistic regression analysis showed that HbA1c level and ERαgene XbaI(AG/GG)were significantly correlated with DO(P<0.05).OR_(e1)with pure6.5%≤HbA1c<9.0%was 6.231,and OR_(g1)with XbaI(AG)type alone was 5.384.The interaction OR_(e1g1)was 33.978,when the two were present at the same time,and the interaction coefficientγ=β_(e1g1)/β_(e1)>1,OR_(e1g1)>OR_(e1)×OR_(g1)was a super multiplication model.6.5%≤HbA1c<9.0%and XbaI(AG/GG),HbA1c≥9.0%and XbaI(AG/GG)all had positive interaction(allγ>1).Conclusion Individuals carrying XbaI(AG)and XbaI(GG)genotypes belong to the high-risk group of DO.

关 键 词：雌激素受体Α基因 糖化血红蛋白 糖尿病性骨质疏松 单核苷酸多态性 交互作用 

分 类 号：R587.2[医药卫生—内分泌] R392.11[医药卫生—内科学]