The role of LRP5-LRP6 gene-gene and gene-environment interactions on the risk of ABM in postmenopausal women with type 2 diabetes mellitus

Abstract

Background: A previous work has discovered that LRP5 and LRP6 locus are linked to the risk of ABM in postmenopausal women with type 2 diabetes mellitus (T2DM). This study aimed to investigate the role of LRP5-LRP6 SNP and gene-gene and gene-environment interactions in the development of ABM in postmenopausal women with type 2 diabetes mellitus . Methods:A total of 272 postmenopausal women, comprising 166 patients with abnormal bone mass (ABM) and 106 controls with normal bone mass, were recruited based on BMD results. BMD of the lumbar spine 1-4 (L1-4) and femoral neck (FN) was measured by dual-energy X-ray (DEXA), and polymorphisms and gene frequency distributions of LRP5 rs2306862, rs41494349, and LRP6 rs10743980, rs2302685 were determined by time-of-flight mass spectrometry (MALDI-TOF MS). Results:1) Logistic regression analysis showed that the risk of ABM was higher for the CT and CT/TT genotypes than for the CC genotype at the rs2306862 locus of the LRP5 gene (OR=2.353, 95%CI=1.039-6.186; OR=2.434, 95%CI=1.071, 5.531; P<0.05). TC genotype at the rs2302685 locus of the LRP6 gene has a higher risk of ABM than TT genotype (OR=2.951, 95%CI=1.030-8.457, P<0.05). 2) Polymorphisms at the rs2306862&rs10743980, rs41494349&rs2302685&rs10743980 SNPs were synergistic with the development of ABM and were risk factors for the development of ABM (P<0.05). Polymorphisms at rs2306862, rs2302685, rs41494349&rs2302685& rs10743980 SNPs were synergistic with the occurrence of ABM and were risk factors for the occurrence of ABM (P<0.05). There was an interaction between gene polymorphism & age at each locus at menopause and the occurrence of ABM (P>0.05). Conclusion:These findings indicate that LRP5-rs2306862 and LRP6-rs2302685 polymorphisms, gene-gene, and gene-age interactions are associated with an increased risk of ABM in postmenopausal women with type 2 diabetes mellitus.