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 TNFRII 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.
Department of Obstetrics and Gynecology, College of Medicine, Seoul National University, Seoul, Korea.
Hoon
H
Kim
Sungwook
S
Chun
Seung Yup
SY
Ku
Chang Suk
CS
Suh
Young Min
YM
Choi
Jung Gu
JG
Kim
D015502:Absorptiometry, Photon; D000368:Aged; D000704:Analysis of Variance; D015519:Bone Density / Q000235:genetics; D016009:Chi-Square Distribution; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007723:Korea / Q000453:epidemiology; D015810:Linkage Disequilibrium / Q000235:genetics; D008233:Lymphotoxin-alpha / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D017698:Postmenopause / Q000235:genetics* / Q000502:physiology; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood / Q000235:genetics*; D012044:Regression Analysis; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics*
D008233:Lymphotoxin-alpha; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha