Association between polymorphisms in tumor necrosis factor (TNF) and TNF receptor genes and circulating TNF, soluble TNF receptor levels, and bone mineral density in postmenopausal Korean women

Objective: 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. Methods: 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. Results: 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 TNFR-H G676C/C1690T haplotype genotype also affected serum sTNFRII levels. Conclusions: 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.Canhao H, 2008, CLIN RHEUMATOL, V27, P301, DOI 10.1007/s10067-007-0706-yKim JG, 2007, MENOPAUSE, V14, P913, DOI 10.1097/gme.0b013e31802d976fLee N, 2007, J GASTROEN HEPATOL, V22, P913, DOI 10.1111/j.1440-1746.2006.04679.xKim JG, 2006, J BONE MINER METAB, V24, P53, DOI 10.1007/s00774-005-0646-zWeitzmann MN, 2005, IMMUNOL REV, V208, P154Chen HY, 2005, EUR J OBSTET GYN R B, V122, P73, DOI 10.1016/j.ejogrb.2005.02.003Moffett SP, 2005, J CLIN ENDOCR METAB, V90, P3491, DOI 10.1210/jc.2004-2235Puga I, 2005, ENDOCRINOLOGY, V146, P2210, DOI 10.1210/en.2004-1366Tasker PN, 2004, OSTEOPOROSIS INT, V15, P903, DOI 10.1007/s00198-004-1617-2Furuta I, 2004, CALCIFIED TISSUE INT, V74, P509, DOI 10.1007/s00223-003-0105-6Kim JG, 2003, AM J OBSTET GYNECOL, V189, P1234, DOI 10.1067/S0002-9378(03)00650-1Albagha OME, 2002, HUM MOL GENET, V11, P2289Ota N, 2002, ANN HUM BIOL, V29, P550, DOI 10.1080/03014460210135730van Heel DA, 2002, HUM MOL GENET, V11, P1281Wennberg P, 2002, EUR J ENDOCRINOL, V146, P629Kim JG, 2002, AM J OBSTET GYNECOL, V186, P345, DOI 10.1067/mob.2002.120483Escobar-Morreale HF, 2001, J CLIN ENDOCR METAB, V86, P3761Payami H, 2001, NEUROLOGY, V56, P1363Kim JG, 2001, MENOPAUSE, V8, P2222001, JAMA, V285, P785Abu-Amer Y, 2000, J BIOL CHEM, V275, P27307Spotila LD, 2000, J BONE MINER RES, V15, P1376Hofbauer LC, 1999, BONE, V25, P255Majetschak M, 1999, ANN SURG, V230, P207Skoog T, 1999, HUM MOL GENET, V8, P1443Pacifici R, 1998, ENDOCRINOLOGY, V139, P2659Higuchi T, 1998, TISSUE ANTIGENS, V51, P605Harris M, 1998, BONE, V22, P141Stuber F, 1996, CRIT CARE MED, V24, P381JOUANNY P, 1995, ARTHRITIS RHEUM, V38, P61KANIS JA, 1994, J BONE MINER RES, V9, P1137DIRENZO GC, 1994, EUR J OBSTET GYN R B, V56, P47BEUTLER B, 1992, AM J MED SCI, V303, P129SARIBAN E, 1988, J CLIN INVEST, V81, P1506