Frequencies of interleukin-6, GST and progesterone receptor gene polymorphisms in postmenopausal women with low bone mineral density
Keywords:
Polymorphism, genetic, Interleukins, Receptors, progesterone, Bone density, PostmenopauseAbstract
CONTEXT AND OBJECTIVE: Osteoporosis is a skeletal disorder characterized by low bone mineral density (BMD). Studies have shown that some of the genetic components relating to lower BMD may be detected by polymorphisms. Our aim was to evaluate the frequencies of interleukin-6, GST and progesterone receptor gene polymorphisms in postmenopausal women with low BMD. DESIGN AND SETTING: Cross-sectional study, conducted in a public university in São Paulo, Brazil. METHODS: We evaluated interleukin-6 (IL-6), progesterone receptor gene (PROGINS) and glutathione S-transferase (GST) polymorphisms in 110 postmenopausal women with no previous use of hormone therapy. Tests were performed using DNA-PCR, from oral scrapings. We used Student’s t-test and a logistic regression model for statistical analysis. RESULTS: Regarding IL-6 polymorphism, 58.2% of the patients were homozygotes (GG) and 41.8% had allele C (heterozygote or mutant homozygote + GC or CC). PROGINS genotype polymorphism was absent in 79% (wild homozygote or P1/P1) and present in 20.9% (heterozygote or P1/P2). Regarding GSTM1 polymorphism, the allele (1/1) was present in 72.7% of the patients and was absent in 27.3%. We found that IL-6 polymorphism had statistically significant correlations with the L2-L4 T-score (P = 0.032) and with BMD (P = 0.005). Women with IL-6 polymorphism were 2.3 times more likely to have a L2-L4 T-score of less than -1, compared with those not presenting this polymorphism. CONCLUSION: IL-6 gene polymorphism was correlated with low BMD, whereas the PROGINS and GSTM1 polymorphisms did not show any correlation.
Downloads
References
Schnatz PF. The 2010 North American Menopause Society position statement: Updates on screening, prevention and management of postmenopausal osteoporosis. Conn Med. 2011;75(8):485-7.
Giroux S, Elfassihi L, Clément V, et al. High-density polymorphisms analysis of 23 candidate genes for association with bone mineral density. Bone. 2010;47(5):975-81.
Singh M, Singh P, Singh S, Juneja PK, Kaur T. A susceptible haplotype within APOE gene influences BMD and intensifies the osteoporosis risk in postmenopausal women of Northwest India. Maturitas. 2010;67(3):239-44.
Richards JB, Kavvoura FK, Rivadeneira F, et al. Collaborative meta- analysis: associations of 150 candidate genes with osteoporosis and osteoporotic fracture. Ann Intern Med. 2009;151(8):528-37.
Chung HW, Seo JS, Hur SE, et al. Association of interleukin-6 promoter variant with bone mineral density in pre-menopausal women. J Hum Genet. 2003;48(5):243-8.
Koh JM, Oh B, Ha MH, et al. Association of IL-15 polymorphisms with bone mineral density in postmenopausal Korean women. Calcif Tissue Int. 2009;85(5):369-78.
Urano T, Shiraki M, Yagi H, et al. GPR98/Gpr98 gene is involved in the regulation of human and mouse bone mineral density. J Clin Endocrinol Metab. 2012;97(4):E565-74.
Lee JS, Suh KT, Eun IS. Polymorphism in interleukin-6 gene is associated with bone mineral density in patients with adolescent idiopathic scoliosis. J Bone Joint Surg Br. 2010;92(8):1118-22.
Dinçel E, Sepici-Dinçel A, Sepici V, Ozsoy H, Sepici B. Hip fracture risk and different gene polymorphisms in the Turkish population. Clinics (Sao Paulo). 2008;63(5):645-50.
Xing L, He GP, Chen YM, Su YX. Interaction of interleukin-6 and estrogen receptor gene polymorphisms on bone mass accrual in Chinese adolescent girls. J Bone Miner Metab. 2008;26(5):493-8.
Fishman D, Faulds G, Jeffery R, et al. The effect of novel polymorphisms in the interleukin-6 (IL6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis. J Clin Invest. 1998;102(7):1369-76.
Hulkkonen J, Pertovaara M, Antonen J, Pasternack A, Hurme M. Elevated interleukin-6 plasma levels are regulated by the promoter region polymorphism of the IL6 gene in primary Sjögren’s syndrome and correlate with the clinical manifestations of the disease. Rheumatology (Oxford). 2001;40(6):656-61.
Nordström A, Gerdhem P, Brändström H, et al. Interleukin-6 promoter polymorphism is associated with bone quality assessed by calcaneus ultrasound and previous fractures in cohort of 75-year-old women. Osteoporos Int. 2004;15(10):820-6.
Ferrari SL, Karasik D, Liu J, et al. Interactions of interleukin-6 promoter polymorphisms with dietary and lifestyle factors and their association with bone mass in men and women from the Framingham Osteoporosis Study. J Bone Miner Res. 2004;19(4):552-9.
Luo XH, Liao EY, Su X. Progesterone upregulates TGF-b isoforms (b1, b2, and b3) expression in normal human osteoblast-like cells. Calcif Tissue Int. 2002;71(4):329-34.
Rowe SM, Coughlan SJ, McKenna NJ, et al. Ovarian carcinoma- associated Taql restriction fragment length polymorphism in intron G of the progesterone receptor gene is due to an Alu sequence insertion. Cancer Res. 1995;55(13):2743-5.
Tong D, Fabjani G, Heinze G, et al. Analysis of the human progesterone receptor gene polymorphism progins in Austrian ovarian carcinoma patients. Int J Cancer. 2001;95(6):394-7.
Rossini A, Rapozo DC, Amorim LM, et al. Frequencies of GSTM1, GSTT1, and GSTP1 polymorphisms in a Brazilian population. Genet Mol Res. 2002;1(3):233-40.
Mlakar SJ, Prezelj J, Marc J. Testing GSTP1 genotypes and haplotypes interactions in Slovenian post-/pre-menopausal women: novel involvement of glutathione S-transferases in bone remodeling process. Maturitas. 2012;71(2):180-7.
Cavalieri EL, Stack DE, Devanesan PD, et al. Molecular origin of cancer: catechol estrogen-3,4-quinoses as endogenous tumor initiators. Proc Natl Acad Sci U S A. 1997;94(20):10937-42.
Seidgård J, Vorachek WR, Pero RW, Pearson WR. Hereditary differences in the expression of the human glutathione transferase active on trans-stilbene oxide are due to a gene deletion. Proc Natl Acad Sci U S A. 1988;85(19):7293-7.
Kiebzak GM, Box JH, Box P. Decreased ulnar bending stiffness in osteoporotic Caucasian women. J Clin Densitom. 1999;2(2):143-52.
Czerny B, Kaminski A, Kurzawski M, et al. The association of IL-1 beta, IL-2, and IL-6 gene polymorphisms with bone mineral density and osteoporosis in postmenopausal women. Eur J Obstet Gynecol Reprod Biol. 2010;149(1):82-5.
Bustamante M, Nogués X, Mellibovsky L, et al. Polymorphisms in the interleukin-6 receptor gene are associated with bone mineral density and body mass index in Spanish postmenopausal women. Eur J Endocrinol. 2007;157(5):677-84.
Garnero P, Borel O, Sornay-Rendu E, et al. Association between a functional interleukin-6 gene polymorphism and peak bone mineral density and postmenopausal bone loss in women: the OFELY study. Bone. 2002;31(1):43-50.
Pilkington MF, Sims SM, Dixon SJ. Transforming growth factor- beta induces osteoclast ruffling and chemotaxis: potential role in osteoclast recruitment. J Bone Miner Res. 2001;16(7):1237-47.
Quinn JM, Itoh K, Udagawa N, et al. Transforming growth factor beta affects osteoclast differentiation via direct and indirect actions. J Bone Miner Res. 2001;16(10):1787-94.
