The aim of this work was to test the association between estrogen receptor α gene (ERα) polymorphism and primary osteoarthritis (OA) of the knee in Mexican mestizo patients. A case–control study was conducted. Cases were patients >40 years of age, with a body mass index (BMI) ≤ 27 and radiologic score for OA of the knee of ≥2 according to Kellgren–Lawrence scale, and controls were subjects >40 years age with a radiologic score <2. Two restriction fragment length polymorphisms, PvuII (T/C; rs2234693), and XbaI (A/G; rs9340799), of the ERα were analyzed. Allelic haplotypes were constructed and non-conditional logistic regression was developed to evaluate risk magnitude through odds ratios (ORs) and 95% Confidence intervals (95% CI). Three different allelic haplotypes were identified: TA; CG, and CA. Unadjusted analysis of the haplotypes did not show significant associations; nonetheless, when data were adjusted for gender, age, and BMI, a significant decrease risk was observed for CG haplotype (OR [95% CI]) = 0.5 (0.3–0.9)] (P = 0.04). These results suggest that ERα gene CG haplotype could be associated with a reduced risk of primary knee OA in Mexican mestizo population.
Osteoarthritis Genetic association Polymorphism Estrogen receptor gene Haplotype
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This work was supported by a grant from the Consejo Nacional de Ciencia y Tecnología (CONACyT), México.
Conflict of interest
The authors declare that they have no conflict of interest.
Spector TD, Cicuttini F, Baker J et al (1996) Genetic influences on osteoarthritis in women: a twin study. Br Med J 312:940–943CrossRefGoogle Scholar
Chitnavis J, Sinsheimer JS, Clipsham K et al (1997) Genetic influences in end-stage osteoarthritis. Sibling risks of hip and knee replacement for idiopathic osteoarthritis. J Bone Joint Surg 79:660–664CrossRefGoogle Scholar
Spector TD, Campion GD (1989) Generalized osteoarthritis: a hormonally mediated disease. Ann Rheum Dis 48:523–527PubMedCrossRefGoogle Scholar
Zhang Y, McAlindon TE, Hannan MT et al (1998) Estrogen replacement therapy and worsening of radiographic knee osteoarthritis: the Framingham Study. Arthritis Rheum 41:1867–1873PubMedCrossRefGoogle Scholar
Thornton JW (2001) Evolution of vertebrate steroid receptors from an ancestral estrogen receptor by ligand exploitation and serial genome expansions. PNAS 98:5671–5676PubMedCrossRefGoogle Scholar
Cheung E, Schwabish MA, Kraus WL (2003) Chromatin exposes intrinsic differences in the transcriptional activities of estrogen receptors α and β. EMBO J 22:600–611PubMedCrossRefGoogle Scholar
Ponglikitmongkol M, Green S, Chambon P (1988) Genomic organization of the human oestrogen receptor gene. EMBO J 7:3385–3388PubMedGoogle Scholar
Kobayashi S, Inoue S, Hosoi T et al (1996) Association of bone mineral density with polymorphism of the estrogen receptor gene. J Bone Miner Res 11:306–311PubMedCrossRefGoogle Scholar
Ushiyama T, Ueyama H, Inoue K et al (1998) Estrogen receptor gene polymorphism and generalized osteoarthritis. J Rheumatol 25:134–137PubMedGoogle Scholar
Bergink AP, van Meurs JB, Loughlin J et al (2003) Estrogen receptor alpha gene haplotype is associated with radiographic osteoarthritis of the knee in elderly men and women. Arthritis Rheum 48:1913–1922PubMedCrossRefGoogle Scholar
Jin SY, Hong S, Yang H et al (2004) Estrogen receptors-α gene haplotypes is associated with primary knee osteoarthritis in Korean population. Arthritis Res Ther 6:415–421CrossRefGoogle Scholar
Loughlin J, Sinsheimer JS, Mustafa Z et al (2000) Association analysis of the vitamin D receptor gene, the type I collagen gene COL1A1, and the estrogen receptor gene in idiopathic osteoarthritis. J Rheumatol 27:779–784PubMedGoogle Scholar
Fytili P, Giannatou E, Papanikolaou V et al (2005) Association of repeat polymorphisms in the estrogen receptors alpha, beta, and androgen receptor genes with knee osteoarthritis. Clin Genet 68:268–277PubMedCrossRefGoogle Scholar
Lian K, Lui L, Zmuda JM et al (2007) Estrogen receptor alpha genotype is associated with a reduced prevalence of radiographic hip osteoarthritis in elderly Caucasian women. Osteoarthritis Cartilage 15:972–978PubMedCrossRefGoogle Scholar
Davidson S, Starkey A, MacKenzie A (2009) Evidence of uneven selective pressure on different subsets of the conserved human genome; implications for the significance of intronic and intergenic DNA. BMC Genomics 10:614–620PubMedCrossRefGoogle Scholar
Wilkins JM, Southam L, Mustafa Z et al (2009) Association of a functional microsatellite within intron 1 of the BMP5 gene with susceptibility to osteoarthritis (Abstract). BMC Medical Genetics 10:141PubMedCrossRefGoogle Scholar
Wang ZY, Zhang XT, Shen P et al (2005) Identification, cloning, and expression of human estrogen receptor-α36, a novel variant of human estrogen receptor-α66. Biochem Biophys Res Commun 336:1023–1027PubMedCrossRefGoogle Scholar
Herrington DM, Howard TD, Brosnihan KB et al (2009) Common estrogen receptor polymorphism augments effects of hormone replacement therapy on E-selectin but not C-reactive protein. Circulation 23(105):1879–1882Google Scholar
Hines LM, Risendal B, Slattery ML et al (2010) Comparative analysis of breast cancer risk factors among Hispanic and non-Hispanic white women. Cancer 116:3215–3223PubMedCrossRefGoogle Scholar
Nakamura T, Shi D, Tzetis M et al (2007) Meta-analysis of association between the ASPN D-repeat and osteoarthritis. Hum Mol Genet 16:1676–1681PubMedCrossRefGoogle Scholar
Cimmino MA, Parodi M (2005) Risk factors for osteoarthritis. Semin Arthritis Rheum 34(Suppl 2):29–34PubMedGoogle Scholar
Hosking L, Lumsden S, Lewis K et al (2004) Detection of genotyping errors by Hardy-Weinberg equilibrium testing. Eur J Hum Genet 12:395–399PubMedCrossRefGoogle Scholar
Herrero-Beaumont G, Román-Blás JA, Castañeda S et al (2009) Primary osteoarthritis no longer primary: three subsets with distinct etiological, clinical, and therapeutic characteristics. Semin Arthritis Rheum 39:71–80PubMedCrossRefGoogle Scholar
Spector TD, Hochberg MC (1994) Methodological problems in the epidemiological study of osteoarthritis. Ann Rheum Dis 53:143–146PubMedCrossRefGoogle Scholar