Kim Hoon, Chun Sungwook, Ku Seung Yup, Suh Chang Suk, Choi Young Min, Kim Jung Gu
Department of Obstetrics and Gynecology, College of Medicine, Seoul National University, Seoul, Korea.
Menopause. 2009 Sep-Oct;16(5):1014-20. doi: 10.1097/gme.0b013e3181a039c8.
The aim of the present study was to investigate the relationship of polymorphisms in the tumor necrosis factor (TNF)-alpha, TNF-beta, and TNF receptor (TNFR) genes to circulating TNF, soluble TNFR (sTNFR) levels, and bone mineral density (BMD) in women.
The TNF-alpha G(-308)A, C(-857)T, C(-863)A, T(-1031)C, TNF-beta A252G, TNFRI A36G, TNFRII T676G, A1663G, A1668G, and C1690T polymorphisms were analyzed in 377 postmenopausal Korean women. The levels of serum TNF-alpha, TNF-beta, sTNFRI, sTNFRII, and bone turnover markers were measured. BMD was examined by dual energy x-ray absorptiometry.
After adjustment for age, body mass index, and years since menopause, no significant differences in BMD of the lumbar spine and femoral neck and serum levels of bone turnover markers were detected, according to single polymorphisms in TNF and TNFR genes and combined polymorphisms. However, the frequencies of the TT genotype of TNF-alpha T(-1031)C polymorphism, the non-AA genotype of TNF-beta A252G polymorphism, and the GG genotype of TNFRII A1663G polymorphism were significantly higher in osteoporotic women than in women with normal BMD, respectively (P < 0.05). The TNFRII T676G polymorphism affected the serum sTNFRI and sTNFRII levels. The serum sTNFRII levels in the CC genotype of TNFRII C1690T polymorphism were the highest, with a G or C allele dose effect, and the TNFRII G676C/C1690T haplotype genotype also affected serum sTNFRII levels.
TNF-alpha T(-1031)C, TNF-beta A252G, and TNFRII A1663G polymorphisms may be genetic factors for osteoporosis in Korean postmenopausal women, and the TNFRII T676G and C1690T polymorphisms and their combined polymorphism affected serum sTNFRII levels. The TNFRII T676G polymorphism also affected the serum sTNFRI levels.
本研究旨在探讨肿瘤坏死因子（TNF）-α、TNF-β及TNF受体（TNFR）基因多态性与女性循环TNF、可溶性TNFR（sTNFR）水平及骨密度（BMD）之间的关系。
对377名绝经后韩国女性进行TNF-α G（-308）A、C（-857）T、C（-863）A、T（-1031）C、TNF-β A252G、TNFRⅠ A36G、TNFRⅡ T676G、A1663G、A1668G及C1690T基因多态性分析。检测血清TNF-α、TNF-β、sTNFRI、sTNFRⅡ水平及骨转换标志物水平。采用双能X线吸收法检测骨密度。
校正年龄、体重指数及绝经年限后，根据TNF和TNFR基因的单基因多态性及联合多态性，未检测到腰椎和股骨颈骨密度及血清骨转换标志物水平有显著差异。然而，TNF-α T（-1031）C多态性的TT基因型、TNF-β A252G多态性的非AA基因型及TNFRⅡ A1663G多态性的GG基因型在骨质疏松女性中的频率分别显著高于骨密度正常女性（P<0.05）。TNFRⅡ T676G多态性影响血清sTNFRI和sTNFRⅡ水平。TNFRⅡ C1690T多态性的CC基因型血清sTNFRⅡ水平最高，存在G或C等位基因剂量效应，且TNFRⅡ G676C/C1690T单倍型基因型也影响血清sTNFRⅡ水平。
TNF-α T（-1031）C、TNF-β A252G及TNFRⅡ A1663G多态性可能是韩国绝经后女性骨质疏松的遗传因素，TNFRⅡ T676G和C1690T多态性及其联合多态性影响血清sTNFRⅡ水平。TNFRⅡ T676G多态性也影响血清sTNFRI水平。
