Techapatiphandee Mananya, Tammachote Nattapol, Tammachote Rachaneekorn, Wongkularb Anna, Yanatatsaneejit Pattamawadee
Human Genetics Research Group, Department of Botany, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand.
Department of Orthopaedics, Faculty of Medicine, Thammasat University Hospital, Khlong Nueng, Pathumthani 12120, Thailand.
Biomed Rep. 2018 Oct;9(4):350-356. doi: 10.3892/br.2018.1137. Epub 2018 Aug 1.
Determining molecular markers for osteoporosis may be valuable for improving the quality of life of affected elderly patients by aiding in early detection and disease management. In the present study, the association between single nucleotide polymorphisms (SNPs) of the vitamin D receptor () and tumour necrosis factor superfamily number 11 () genes and the susceptibility of developing osteoporosis was investigated in a Thai female cohort. The study group consisted of 105 Thai postmenopausal patients diagnosed with osteoporosis and 132 healthy Thai postmenopausal female volunteers. DNA extracted from blood samples was used to genotype the and genes using polymerase chain reaction-restriction fragment length polymorphism and sequencing analysis. For , the frequencies of the genotypes TT, CT and CC for the I SNP (rs731236) were 87.88, 11.36 and 0.76%, respectively, in the control group, while in the osteoporosis cohort were 92.38, 5.71 and 1.91%, respectively. For the I SNP (rs2228570), the frequencies of the genotypes CC, CT and TT were 31.06, 55.30 and 13.64%, respectively, in the control group, and in the osteoporosis group were 29.52, 43.81 and 26.67%, respectively. For I SNP (rs1544410), the frequencies of the genotypes GG, GA and AA were 78.03, 18.94 and 3.03%, respectively, in control group, and in the osteoporosis group were 80.95, 18.10 and 0.95%, respectively. The significant risk of osteoporosis associated with the I SNP was determined. The odds ratio (95% confidence interval) was 2.30 (1.14-4.69; P=0.01) among patients with osteoporosis with TT as the susceptibility genotype. For , the frequencies of the genotypes TT, CT and CC for the -290C>T SNP (rs9525641) in the control group were 36.36, 50.76 and 12.88%, respectively, while in the osteoporosis group were 31.43, 56.19 and 12.38%, respectively. For the -643C>T SNP (rs9533156), the frequencies of the genotypes TT, CT and CC in the control group were 35.61, 48.48 and 15.91%, respectively, while in the osteoporosis group were 32.38, 55.24 and 12.38%, respectively. For the -693G>C SNP (rs9533155), the frequencies of the genotypes CC, CG, and GG in the control group were 39.39, 46.97 and 13.64%, respectively, and in the osteoporosis group were 36.19, 53.33 and 10.48%, respectively. No significant associations of the SNPs with osteoporosis were determined; however, it was notable that the GCT haplotype of may be a protective haplotype for osteoporosis. Therefore, it was concluded that the SNP I of may be a potential molecular biomarker for the development of osteoporosis in Thai females.
确定骨质疏松症的分子标志物对于改善受影响老年患者的生活质量可能具有重要价值，有助于早期检测和疾病管理。在本研究中，在泰国女性队列中研究了维生素D受体（VDR）和肿瘤坏死因子超家族成员11（TNFSF11）基因的单核苷酸多态性（SNP）与发生骨质疏松症易感性之间的关联。研究组由105名被诊断为骨质疏松症的泰国绝经后患者和132名健康的泰国绝经后女性志愿者组成。从血样中提取的DNA用于通过聚合酶链反应-限制性片段长度多态性和测序分析对VDR和TNFSF11基因进行基因分型。对于VDR，对照组中I SNP（rs731236）的基因型TT、CT和CC的频率分别为87.88%、11.36%和0.76%，而在骨质疏松症队列中分别为92.38%、5.71%和1.91%。对于I SNP（rs2228570），对照组中基因型CC、CT和TT的频率分别为31.06%、55.30%和13.64%，在骨质疏松症组中分别为29.52%、43.81%和26.67%。对于I SNP（rs1544410），对照组中基因型GG、GA和AA的频率分别为78.03%、18.94%和3.03%，在骨质疏松症组中分别为80.95%、18.10%和0.95%。确定了与I SNP相关的骨质疏松症的显著风险。在以TT为易感基因型的骨质疏松症患者中，优势比（95%置信区间）为2.30（1.14 - 4.69；P = 0.01）。对于TNFSF11，对照组中-290C>T SNP（rs9525641）的基因型TT、CT和CC的频率分别为36.36%、50.76%和12.88%，而在骨质疏松症组中分别为31.43%、56.19%和12.38%。对于-643C>T SNP（rs9533156），对照组中基因型TT、CT和CC的频率分别为35.61%、48.48%和15.91%，在骨质疏松症组中分别为32.38%、55.24%和12.38%。对于-693G>C SNP（rs9533155），对照组中基因型CC、CG和GG的频率分别为39.39%和13.64%，在骨质疏松症组中分别为36.19%、53.33%和10.48%。未确定TNFSF11的SNP与骨质疏松症之间的显著关联；然而，值得注意的是，TNFSF11的GCT单倍型可能是骨质疏松症的一种保护单倍型。因此，得出结论，VDR的SNP I可能是泰国女性骨质疏松症发生的潜在分子生物标志物。
