3'-UTR Polymorphisms of MTHFR and TS Associated with Osteoporotic Vertebral Compression Fracture Susceptibility in Postmenopausal Women.

Tae-Keun Ahn,Han Park,In Han,Jeong Shim,Hyun Kim,Nam Kim,Alexander Ropper,Jung Kim

doi:10.3390/ijms19030824

Abstract

Postmenopausal osteoporosis is one of the most prominent diseases in postmenopausal women and it is increasing in prevalence with the aging population. Furthermore, osteoporosis and osteoporotic vertebral compression fractures (OVCFs) are related to mortality and decreased quality of life. Therefore, searching for biomarkers that are able to identify postmenopausal women who are at high risk of developing OVCFs is an effective strategy for improving the quality of life of patients and alleviating social and economic burdens. In this study, we investigated methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TS) gene polymorphisms in postmenopausal women with OVCF. We recruited 301 postmenopausal women and performed genotyping for the presence of MTHFR 2572C>A, 4869C>G and TS 1100C>T, 1170A>G. Genotyping was analyzed using the polymerization chain reaction restriction fragment length polymorphism assay. MTHFR 2572C>A and TS 1100C>T were associated with the prevalence of osteoporosis (MTHFR 2572CC versus CA+AA: odd ratio [OR] adjusted age, hypertention [HTN], and diabetes mellitus [DM] = 0.49, p = 0.012) and the occurrence of OVCFs (MTHFR 2572CC versus CA+AA: OR adjusted age, HTN, and DM = 0.38, p = 0.013; TS 1100CC versus CT+TT: OR adjusted age, HTN, and DM = 0.46, p = 0.02). Our novel finding is the identification of MTHFR and TS genetic variants that decrease susceptibility to OVCFs. Our findings suggest that polymorphisms in the MTHFR and TS genes are associated with susceptibility to osteoporosis and OVCFs in postmenopausal women.

Highlights

Osteoporosis is a systemic skeletal disorder characterized by low bone mass and a deterioration of bone structure, both of which are associated with bone fragility and increased fracture risk [1]
Sci. 2018, 19, 824 the control group with the osteoporosis and osteoporotic vertebral compression fractures (OVCFs) groups, we found that the patients with osteoporosis and OVCF were significantly more likely to have high blood glucose, decreased folate levels, and low body mass index (BMI)
Our results show that methylenetetrahydrofolate reductase (MTHFR) 2572CA+AA is significantly associated with a decreased risk of osteoporosis and OVCF and that the allele combination of MTHFR 2572A-4869G is significantly associated with a decreased risk of osteoporosis

Summary

Introduction

Osteoporosis is a systemic skeletal disorder characterized by low bone mass and a deterioration of bone structure, both of which are associated with bone fragility and increased fracture risk [1]. Previous studies have presented various factors associated with the occurrence of osteoporosis, including aging, obesity, prior fractures, smoking status, metabolic disorders of vitamin B12, genetic variants, and postmenopausal estrogen deficiency [2]. Menopause elicits changes in homeostatic regulation as indicated by reduced reproductive hormone levels, abnormal metabolism, and increased total homocysteine (tHcy) levels, all of which are related to an elevated occurrence of osteoporosis [4,5]. An elevated plasma concentration of tHcy has been associated with an increased risk of osteoporotic fractures [7,8,9]. Some in vivo studies have reported that Hcy stimulates osteoclast differentiation and induces apoptosis of osteoblast-lineage cells [10,11]

Methods

Results

Discussion

Conclusion