Polymorphisms of miR‐146a, miR‐149, miR‐196a2, and miR‐499 are associated with osteoporotic vertebral compression fractures in Korean postmenopausal women. Issue 1 (11th August 2017)

• Record Type: Journal Article
• Authors: Ahn, Tae‐Keun; Kim, Jung‐Oh; Kumar, Hemant; Choi, Hyemi; Jo, Min‐Jae; Sohn, Seil; Ropper, Alexander E.; Kim, Nam‐Keun; Han, In‐Bo
• Is Part Of: Journal of orthopaedic research. Volume 36:Issue 1(2018)
• Page Start: 244
• Page End: 253
• Publication Date: 2017-08-11
• Subjects: osteoporosis -- osteoporotic vertebral compression fracture -- postmenopausal women -- microRNA -- single nucleotide polymorphism; Orthopedics -- Periodicals; Musculoskeletal system -- Periodicals; 616.7
• DOI: 10.1002/jor.23640
• Languages: English
• ISSNs: 0736-0266

Abstract

ABSTRACT: Genetic factors have been shown to be a small but significant predictor for osteoporosis and osteoporotic fracture risk. We performed a case–control association study to determine the association between miR‐146a, miR‐149, miR‐196a2, and miR ‐499 polymorphisms and osteoporotic vertebral compression fracture (OVCF) susceptibility. In total, 286 unrelated postmenopausal Korean women (57 with OVCFs, 55 with non‐OVCFs, and 174 healthy controls) were recruited. All subjects underwent dual energy X‐ray absorptiometry to determine BMD at the lumbar spine and femoral neck. We focused on four single nucleotide polymorphisms (SNPs) of pre‐miRNA sequences including miR‐146a C>G (rs2910164), miR‐149 T>C (rs2292832), miR‐196a2 T>C (rs11614913), and miR ‐ 499 A>G (rs3746444). Genotype frequencies of these four SNPs were determined using polymerase chain reaction‐restriction fragment length polymorphism analysis. The TT genotype of miR ‐ 149a T>C was less frequent in subjects with OVCFs, suggesting a protective effect against OVCF risk (Odds ratio [OR], 0.435; 95% confidence interval [CI], 0.22–0.85, p = 0.014), whereas the miR‐146a CG / miR‐196a2 TC combined genotype was more frequent in OVCF patients (OR, 5.163; 95%CI, 1.057–25.21, p = 0.043), suggesting an increase in OVCF risk. Additionally, combinations of miR‐146a, ‐149, ‐196a2, and ‐ 449 showed a significant association with increased prevalence of OVCFs in postmenopausal women. In particular, the miR‐146a G /‐149 T /‐196a2 C /‐449 G allele combination was significantly associated with an increased risk of OVCF (OR, 35.01; 95% CI, 1.919–638.6, p = 0.001). Our findings suggest that the TT genotype of miR ‐ 149a T>C may contribute to decreased susceptibility to OVCF in Korean postmenopausal women. Conversely, the miR‐146a CG / miR‐196a2 TC combined genotype and the miR‐146a G /‐149 T /‐196a2 C /‐449 G allele combination may contribute to increased susceptibility to OVCF. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:244–253, 2018.