转录因子7类似物2基因多态性及表达在绝经后2型糖尿病合并骨质疏松中的作用

Study on the mechanism of TCF7L2 gene polymorphism and expression level in postmenopausal type 2 diabetes with osteoporosis

Objective To investigate the role of TCF7L2 gene polymorphism and related mechanisms in postmenopausal women with type 2 diabetes mellitus(T2DM)who are at high risk for osteoporosis(OP).Methods 148 postmenopausal women with T2DM from Jan.2019 to Jun.2020 were selected as study subjects.Among them,86 patients combined with OP(T2DM+0P group)and 62 patients without OP(T2DM group)were included,and 100 healthy postmenopausal women who underwent physical examination in our hospital during the same period were included as the control group.Fasting venous blood was extracted to detect clinical and bone metabolism indicators.Two SNP sites of TCF7L2,rs7901695(T>C)and rs290487(C>T),were genotyped by capillary electrophoresis and section analysis(SNaPshot).The relative mRNA expression of TCF7L2 gene was determined by quantitative real-time fluorescence quantitative PCR assay.To investigate the effects of overexpression and silencing of TCF7L2 on proliferation of rat osteoblasts,lentiviral vectors were constructed.Results For rs7901695,TT,TC and CC genotypes in T2DM+0P group,T2DM group and control group were significantly different(X²=12.545,P=0.014),and the frequency distribution of T and C alleles was significantly different among the three groups(X²=17.089,P<0.001).For RS290487,CC,CT and TT genotypes of T2DM+OP group,T2DM group and control group were significantly different(X^2=10.500,P=0.033),and the frequency distribution of C and T alleles was significantly different among the three groups(X²=14.665,P=0.001).For rs7901695,FPG and TG levels in T2DM+OP patients with CC+TC genotype were significantly higher than those with wild-type TT genotype(FPG:t=2.559,P=0.014;TG:t=2.034,P=0.036),while serum calcium and 25OHD3 levels were significantly lower than those with Wild-type TT genotype(calcium:t=3.889,P