Study on the mechanism of TCF7L2 gene polymorphism and expression level in postmenopausal type 2 diabetes with osteoporosis / 中华内分泌外科杂志

ABSTRACT

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+OP 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+OP group, T2DM group and control group were significantly different ( χ2=12.545, P=0.014) , and the frequency distribution of T and C alleles was significantly different among the three groups ( χ2=17.089, P<0.001) . For RS290487, CC, CT and TT genotypes of T2DM+OP group, T2DM group and control group were significantly different ( χ2=10.500, P=0.033) , and the frequency distribution of C and T alleles was significantly different among the three groups ( χ2=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<0.001; 25OHD t=4.112, P<0.001) . For rs290487 site, serum calcium, BGP and 25OHD3 levels in T2DM+OP patients with TT+CT genotype were significantly lower than those with wild-type CC genotype, and the difference was statistically significant (calcium t=3.751, P<0.001; BGP 2.731, P=0.007; 25OHD3 t=3.225, P=0.002) . The relative mRNA expression level of TCF7L2 gene in T2DM+OP patients was significantly lower than that in T2DM group and the control group ( F=5.735, P<0.05) . With the increase of Allele C at rs7901695, the relative mRNA expression level of TCF7L2 gene decreased gradually ( F=5.723, P<0.05) . In addition, the proliferation rate of rat osteoblasts overexpressed by TCF7L2 was significantly increased, while the proliferation level of TCF7L2 silenced osteoblasts was significantly decreased ( F=7.846, P<0.05) . Conclusion:In postmenopausal WOMEN with T2DM, the variation of TCF7L2 gene will lead to the decrease of gene expression level, and the suppression of osteoblasts proliferation, thus participate in the pathogenesis of OP.