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

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.

Homocysteine: Its Possible Emerging Role in At-Risk Population Groups

“…MTHFR polymorphism C667 T could also be involved in the increase of osteoporotic fracture incidence [181], and a recently published meta-analysis showed an association between MTHFR C667 T polymorphism and reduced bone mineral density in the lumbar spine and femoral neck in Caucasians, post-menopausal women, and men, and with total BMD in women [185]. Ahn et al [186] reported an association in 301 postmenopausal women between osteoporotic vertebral compression fractures and MTHFR and TS gene polymorphisms in the 3 -UTR region. Concerning the effect of supplementation, a systematic review with meta-analysis [187] concluded that vitamin B12 status may be associated with fracture risk, and evidence for an association between folate status and fracture risk is scarce.…”

Therapeutic effect of percutaneous kyphoplasty combined with anti-osteoporosis drug on postmenopausal women with osteoporotic vertebral compression fracture and analysis of postoperative bone cement leakage risk factors: a retrospective cohort study

“…Patients with osteoporosis can suffer from fracture when subjected to low-energy shock due to the increased bone fragility, and the fractures are often found in the pelvis, vertebrae, hip, and proximal humerus, clinically known as osteoporotic vertebral compression fracture (OVCF) [9]. The incidence of OVCF in women is significantly higher than that in men, especially in postmenopausal women, which may be associated with changes in estrogen levels of postmenopausal women [10]. The clinical manifestations of OVCF are mainly unbearable pain and inability to walk, which severely affects the quality of life of patients, and some patients with OVCF have mental disorder and venous thrombosis [11].…”

3’-UTR Polymorphisms of Vitamin B-Related Genes Are Associated with Osteoporosis and Osteoporotic Vertebral Compression Fractures (OVCFs) in Postmenopausal Women

“…Lastly, we should consider the possible changes of analyzed genes due to change in miRNA action because we investigated SNPs located in 3´–UTR of B vitamin–related genes. Genetic variation in the 3´–UTR can affect gene expression by interfering with miRNA binding [ 12 , 37 , 38 ]. Polymorphisms residing within the miRNA–binding site of the target genes may have their own disease onset effect, but changes in the miRNA binding efficiency also has to be considered [ 23 , 24 ].…”

“…For example, a single nucleotide polymorphism (SNPs) in methylenetetrahydrofolate reductase ( MTHFR 677 C>T) has been shown to be associated with BMD [ 10 , 11 ]. Recently, it was also reported that SNPs in the 3´ untranslated regions (UTRs) of MTHFR (2572 C>A) and thymidylate synthase (1100 C>T) are associated with the prevalence of osteoporosis and osteoporotic vertebral compression fractures (OVCFs) [ 12 ].…”