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. 1999 Aug;58(8):500–502. doi: 10.1136/ard.58.8.500

Polymorphic CAG repeats of the androgen receptor gene and rheumatoid arthritis

T Kawasaki 1, T Ushiyama 1, H Ueyama 1, K Inoue 1, K Mori 1, I Ohkubo 1, S Hukuda 1
PMCID: PMC1752923  PMID: 10419869

Abstract

OBJECTIVE—In view of the possible role of androgens in the pathogenesis of rheumatoid arthritis (RA), this study investigated the association between repeat lengths of CAG microsatellites of the androgen receptor (AR) gene and RA.
METHODS—The number of CAG repeats in exon 1 of the AR gene was determined in 90 men and 276 women with RA, as well as in 305 male and 332 female controls.
RESULTS—The male RA patients tended to have shorter repeats than the male controls (22.5 versus 23.1, p=0.07), whereas the female RA patients had similar repeats to the female controls (22.7 versus 22.9, p=0.17). Patients of both sexes were divided into younger and older age at onset groups, and compared with younger and older controls. Younger onset male RA patients had significantly shorter CAG repeat lengths than the younger male controls (21.8 versus 23.2, p=0.007) or the older onset male RA patients (21.8 versus 23.2, p=0.04). Older onset male RA and both younger and older onset female RA patients had similar CAG repeat lengths when compared with their controls. Neither seropositivity nor rheumatoid nodule positivity had a significant relation with CAG repeat lengths.
CONCLUSION—Shorter CAG repeats of the AR gene, presenting high levels of transactivation activity, are related to younger age onset male RA, suggesting the possible role of androgens as a modulating factor.



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Selected References

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  1. Arnett F. C., Edworthy S. M., Bloch D. A., McShane D. J., Fries J. F., Cooper N. S., Healey L. A., Kaplan S. R., Liang M. H., Luthra H. S. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988 Mar;31(3):315–324. doi: 10.1002/art.1780310302. [DOI] [PubMed] [Google Scholar]
  2. Chamberlain N. L., Driver E. D., Miesfeld R. L. The length and location of CAG trinucleotide repeats in the androgen receptor N-terminal domain affect transactivation function. Nucleic Acids Res. 1994 Aug 11;22(15):3181–3186. doi: 10.1093/nar/22.15.3181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cutolo M., Accardo S. Sex hormones, HLA and rheumatoid arthritis. Clin Exp Rheumatol. 1991 Nov-Dec;9(6):641–646. [PubMed] [Google Scholar]
  4. Cutolo M. Do sex hormones modulate the synovial macrophages in rheumatoid arthritis? Ann Rheum Dis. 1997 May;56(5):281–284. doi: 10.1136/ard.56.5.281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cutolo M., Masi A. T. Do androgens influence the pathophysiology of rheumatoid arthritis? Facts and hypotheses. J Rheumatol. 1998 Jun;25(6):1041–1047. [PubMed] [Google Scholar]
  6. Giovannucci E., Stampfer M. J., Krithivas K., Brown M., Dahl D., Brufsky A., Talcott J., Hennekens C. H., Kantoff P. W. The CAG repeat within the androgen receptor gene and its relationship to prostate cancer. Proc Natl Acad Sci U S A. 1997 Apr 1;94(7):3320–3323. doi: 10.1073/pnas.94.7.3320. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Irvine R. A., Yu M. C., Ross R. K., Coetzee G. A. The CAG and GGC microsatellites of the androgen receptor gene are in linkage disequilibrium in men with prostate cancer. Cancer Res. 1995 May 1;55(9):1937–1940. [PubMed] [Google Scholar]
  8. Iványi P., Hámpl R., Stárka L., Micková M. Genetic association between H-2 gene and testosterone metabolism in mice. Nat New Biol. 1972 Aug 30;238(87):280–281. doi: 10.1038/newbio238280a0. [DOI] [PubMed] [Google Scholar]
  9. Masi A. T. Sex hormones and rheumatoid arthritis: cause or effect relationships in a complex pathophysiology? Clin Exp Rheumatol. 1995 Mar-Apr;13(2):227–240. [PubMed] [Google Scholar]
  10. Mhatre A. N., Trifiro M. A., Kaufman M., Kazemi-Esfarjani P., Figlewicz D., Rouleau G., Pinsky L. Reduced transcriptional regulatory competence of the androgen receptor in X-linked spinal and bulbar muscular atrophy. Nat Genet. 1993 Oct;5(2):184–188. doi: 10.1038/ng1093-184. [DOI] [PubMed] [Google Scholar]
  11. Ollier W., Spector T., Silman A., Perry L., Ord J., Thomson W., Festenstein H. Are certain HLA haplotypes responsible for low testosterone levels in males? Dis Markers. 1989 Jul-Sep;7(3):139–143. [PubMed] [Google Scholar]
  12. Payne A. H. Hormonal regulation of cytochrome P450 enzymes, cholesterol side-chain cleavage and 17 alpha-hydroxylase/C17-20 lyase in Leydig cells. Biol Reprod. 1990 Mar;42(3):399–404. doi: 10.1095/biolreprod42.3.399. [DOI] [PubMed] [Google Scholar]
  13. Roselli C. E., Resko J. A. Sex differences in androgen-regulated expression of cytochrome P450 aromatase in the rat brain. J Steroid Biochem Mol Biol. 1997 Apr;61(3-6):365–374. [PubMed] [Google Scholar]
  14. Silman A. J., MacGregor A. J., Thomson W., Holligan S., Carthy D., Farhan A., Ollier W. E. Twin concordance rates for rheumatoid arthritis: results from a nationwide study. Br J Rheumatol. 1993 Oct;32(10):903–907. doi: 10.1093/rheumatology/32.10.903. [DOI] [PubMed] [Google Scholar]
  15. Stanford J. L., Just J. J., Gibbs M., Wicklund K. G., Neal C. L., Blumenstein B. A., Ostrander E. A. Polymorphic repeats in the androgen receptor gene: molecular markers of prostate cancer risk. Cancer Res. 1997 Mar 15;57(6):1194–1198. [PubMed] [Google Scholar]
  16. Ushiyama T., Mori K., Inoue K., Huang J., Nishioka J., Hukuda S. Association of oestrogen receptor gene polymorphisms with age at onset of rheumatoid arthritis. Ann Rheum Dis. 1999 Jan;58(1):7–10. doi: 10.1136/ard.58.1.7. [DOI] [PMC free article] [PubMed] [Google Scholar]

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