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Association of a cytosine-adenine repeat polymorphism in the estrogen receptor <i>β</i> gene with occurrence and severity of rheumatoid arthritis

¹ Department of Geriatric Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan
² Department of Geriatric Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan
³ Department of Geriatric Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan
⁴ Department of Geriatric Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan
⁵ Assessment Area, Medicines for Veterinary Use Department, Agencia Espa?ola de Medicamentosy Productos Sanitarios (AEMPS), Madrid, Spain
⁶ Department of Geriatric Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan
⁷ Research Center for Frontier Medical Engineering, Chiba University, Chiba, Japan
⁸ Department of Frontier Japanese-Oriental (Kampo) Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan
⁹ Department of Geriatric Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan

Open Journal of Internal Medicine·Volume 03 (2013)·Pages 3–7·Published 22 March 2013·DOI10.4236/ojim.2013.31002

Abstract

We investigated the influence of the cytosine-adenine (CA) dinucleotide repeat polymorphism in intron 6 of estrogen receptor β (ER β ) gene on rheumatoid arthritis (RA) risk. One hundred and ninety-three RA patients and 77 control subjects with osteoarthritis (OA) were recruited. The CA repeat polymorphism was assayed by a dye-terminator cycle sequencing analysis. No statistically significant difference in the mean num ber of CA repeats between the RA and OA patients was observed (RA: 21.47, OA: 21.23, P = 0.324). The alleles were categorized according to the number of repeats: short (S, ≦21) and long (L, ≧22), in which the genotypes SS, SL, and LL were observed. No significant differences were observed for the allele and genotype distributions of this polymorphism in both patient groups. The RA patients were classified ac cording to RA severity: mild (least erosive disease) and severe (more erosive and mutilating disease). Again, no significant difference in genotype frequency between these groups was observed, even after stratifying by sex. The present study indicates that additional studies are needed to clarify the roles of this polymorphism, estrogen, and ER in the development of autoimmune diseases.

KeywordsPolymorphismRheumatoid ArthritisSexEstrogen Receptor &lti&gtβ&lt/i&gtCA Repeat

Harle, P., Bongartz, T., Scholmerich, J., Müller-Ladner, U. and Straub, R.H. (2005) Predictive and potentially predictive factors in early arthritis: A multidisciplinary approach. Rheumatology (Oxford), 44, 426-433. doi:10.1093/rheumatology/keh530
Klareskog, L., Catrina, A.I. and Paget, S. (2009) Rheumatoid arthritis. Lancet, 373, 659-672. doi:10.1016/S0140-6736(09)60008-8
Whitacre, C.C. (2001) Sex differences in autoimmune disease. Nature Immunology, 2, 777-780. doi:10.1038/ni0901-777
Cutolo, M., Straub, R.H. and Bijlsma, J.W. (2007) Neuroendocrine-immune interactions in synovitis. Nature Clinical Practice. Rheumatology, 3, 627-634. doi:10.1038/ncprheum0601
Nelson, J.L. and Ostensen, M. (1997) Pregnancy and rheumatoid arthritis. Rheumatic Diseases Clinics of North America, 23, 195-212. doi:10.1016/S0889-857X(05)70323-9
Kuiper, S., van Gestel, A.M., Swinkels, H.L., de Boo, T.M., da Silva, J.A. and van Riel, P.L. (2001) Influence of sex, age, and menopausal state on the course of early rheumatoid arthritis. The Journal of Rheumatology, 28, 1809-1816.
Mosselman, S., Polman, J. and Dijkema, R. (1996) ERβ: Identification and characterization of a novel human estrogen receptor. FEBS Letters, 392, 49-53. doi:10.1016/0014-5793(96)00782-X
Dietrich, W., Haitel, A., Holzer, G., Huber, J.C., Kolbus, A. and Tschugguel, W. (2006) Estrogen receptor-β is the predominant estrogen receptor subtype in normal human synovia. Journal of the Society for Gynecologic Investigation, 13, 512-517.
Ishizuka, M., Hatori, M., Suzuki, T., Miki, Y., Darnel, A.D., Tazawa, C., Sawai, T., Uzuki, M., Tanaka, Y., Kokubun, S. and Sasano, H. (2004) Sex steroid receptors in rheumatoid arthritis. Clinical Science, 106, 293-300. doi:10.1042/CS20030317
Fytili, P., Giannatou, E., Papanikolaou, V., Stripeli, F., Karachalios, T., Malizos, K. and Tsezou, A. (2005) Association of repeat polymorphisms in the estrogen receptors α, β, and androgen receptor genes with knee osteoarthritis. Clinical Genetics, 68, 268-277. doi:10.1111/j.1399-0004.2005.00495.x
Shearman, A.M., Karasik, D., Gruenthal, K.M., Demissie, S., Cupples, L.A., Housman, D.E. and Kiel, D.P. (2004) Estrogen receptor beta polymorphisms are associated with bone mass in women and men: The Framingham Study. Journal of Bone and Mineral Research, 19, 773-781. doi:10.1359/jbmr.0301258
Negishi, E., Takeo, C., Nakajima, A., Hisamitsu, K., Amano, K., Hirai, A. and Ueno, K. (2006) Analysis of correlation between prescription drugs for climacteric disorders and CA repeat polymorphism of estrogen receptor β gene. Japanese Journal of Pharmaceutical Health Care and Sciences, 32, 21-26. doi:10.5649/jjphcs.32.21

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Association of a cytosine-adenine repeat polymorphism in the estrogen receptor <i>β</i> gene with occurrence and severity of rheumatoid arthritis

Abstract

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