Quantitative Assessment of the Association between Polymorphisms in Osteoprotegerin Gene and Risk of Low Bone Mineral Density

Abstract

Background: Low bone mineral density (BMD) predisposes to os-teoporosis and elevated risk of fractures. Osteoprotegerin is a soluble molecule associated to metabolism of bone tissue with inhibition of osteoclast-differentiation. Several studies determined the relation among polymorphisms in osteoprotegerin gene and low BMD, but the results are contradictory, so an evaluation about these polymorphisms is necessary. This study carried out a meta-analysis to four polymor-phisms in osteoprotegerin gene (A163G, G1181C, T950C, T245G). Methods: A search in literature was made to identify studies with relevant information. The data was extracted by two investigators independently, following a standardized form. The statistical software Review Manager version 5.2 was used to calculation of heterogeneity (I²), Odds Ratio (OR) and Funnel plots with P<0.05. Results: Nineteen papers with twenty-one eligible studies with 5,120 patients and 4,386 controls were identified. G allele was associated to case group in A163G, G1181C and T245G polymorphisms (OR = 1.27, 95% CI 1.10, 1.46, P = 0.0010; OR = 1.25, 95% CI 1.14, 1.37, P < 0.00001; OR = 1.24, 95% CI 1.05, 1.48, P = 0.01, respectively). In T950C polymorphism, T allele neither C allele was associated to risk of bone low mineral density. No bias of publication was found in this analysis. Rerefences 1. Gnudi S, Sitta E, Fiumi N: Relationship between body composition and bone mineral density in women with and without osteoporosis: relative contribution of lean and fat mass. J Bone Miner Metab 2007, 25(5):326. 2. Jian WX, Long JR, Li MX, Liu XH, Deng HW: Genetic determination of variation and covariation of bone mineral density at the hip and spine in a Chinese population. J Bone Miner Metab 2005, 23(2):181-185. 3. Hussien YM, Shehata A, Karam RA, Alzahrani SS, Magdy H, El-Shafey AM: Polymorphism in vitamin D receptor and osteoprotegerin genes in Egyptian rheumatoid arthritis patients with and without osteoporosis. Mol Biol Rep 2013, 40:3675-3680. 4. Panach L, Mifsut D, Tarín JJ, Cano A, García-Pérez MÁ: Replication study of three functional polymorphisms associated with bone mineral density in a cohort of Spanish women. J Bone Miner Metab 2014, 32(6):691-698. 5. Horst-Sikorska W, Kalak R, Wawrzyniak A, Marcinkowska M, Celczynska-Bajew L, Slomski R: Association analysis of the polymorphisms of the VDR gene with bone mineral density and the occurrence of fractures. J Bone Miner Metab 2007, 25(5):310-319. 6. Yu F, Huang X, Miao J, Guo L, Tao D: Association between osteoprotegerin genetic variants and osteoporosis in Chinese postmenopausal women. Endocr J 2013, 60(12):1303-1307. 7. Nakashima T, Takayanagi H: Osteoclasts and the immune system. J Bone Miner Metab 2009, 27(5):519-529. 8. Wu ZZ, Liu M: The effect of low-body weight combined with T149C and A163G polymorphism of osteoprotegerin promoter region on osteoporosis. Chin J Geriatr 2006, 25:645-650. 9. Shui MM, Na SP, Xie RJ, Wang MG, Mu SH: Relationship between the polymorphisms of T149C and T950C in osteoprotegerin gene and the...

Osteoprotegerin genetic polymorphisms and their influence on therapeutic response to ibandronate in postmenopausal osteoporotic females

“…T245G (rs3134069). This SNP is present in the promoter region (5 0 UTR) of the TNFRSF11B (OPG) gene for analysis; such polymorphism is associated with osteoporosis and other bone-related conditions [9,17].…”

“…Another study suggested that the OPG/A163G polymorphism participates in the genetic control of bone homeostasis among the Slovak population and can raise or lower the risk of osteoporosis in such individuals [ 7 ]. Different meta-analyses (MA) have shown that the G allele of the OPG A163G and T245G polymorphisms might increase osteoporosis risk [ 8 , 9 ]. One interesting study displayed that A163G and T245G were linked to augmented fracture risk.…”

“…A recent study reported that genetic polymorphisms in the VDR gene may affect the effectiveness of ibandronate and raloxifene treatment osteoporotic females [11]. Similarly, several types of polymorphism in OPG gene are associated with fracture risk in osteoporotic female patients [8,9]. A number of studies have also reported the age and body mass index BMI relationship with BMD [12][13][14].…”