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Annals of the Rheumatic Diseases logoLink to Annals of the Rheumatic Diseases
. 1991 Jun;50(6):401–404. doi: 10.1136/ard.50.6.401

Sex ratios and hormones in HLA related rheumatic diseases.

W H James 1
PMCID: PMC1004447  PMID: 2059084

Abstract

The major diseases associated with HLA-B27 (Reiter's disease, ankylosing spondylitis, acute anterior uveitis, and psoriatic arthritis) all occur much more commonly in men. Published evidence indicates that the antigen HLA-B27 is associated with high testosterone concentrations in men. Moreover, the antigen HLA-B44 exerts a protective effect on one of these diseases (psoriatic arthritis), and there are external grounds for supposing that HLA-B44 indexes an antiandrogenic process. These data are interpreted as support for the hypothesis (first adumbrated nearly 20 years ago) that HLA antigens index unusual hormone concentrations, which in turn are causally related to the diseases. An examination of published reports suggests that sibs of probands with ankylosing spondylitis (and perhaps Reiter's disease) contain an excess of men, and that sibs of probands with rheumatoid arthritis contain an excess of women. These data lend further support to the hypothesis.

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Selected References

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  1. Aaron S., Fraser P. A., Jackson J. M., Larson M., Glass D. N. Sex ratio and sibship size in juvenile rheumatoid arthritis kindreds. Arthritis Rheum. 1985 Jul;28(7):753–758. doi: 10.1002/art.1780280705. [DOI] [PubMed] [Google Scholar]
  2. BARTER R. W. Familial incidence of rheumatoid arthritis and acute rheumatism in 100 rheumatoid arthritics. Ann Rheum Dis. 1952 Mar;11(1):39–46. doi: 10.1136/ard.11.1.39. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brewerton D. A., Caffrey M., Nicholls A., Walters D., Oates J. K., James D. C. Reiter's disease and HL-A 27. Lancet. 1973 Nov 3;302(7836):996–998. doi: 10.1016/s0140-6736(73)91091-x. [DOI] [PubMed] [Google Scholar]
  4. CSONKA G. W. The course of Reiter's syndrome. Br Med J. 1958 May 10;1(5079):1088–1090. doi: 10.1136/bmj.1.5079.1088. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cutolo M., Balleari E., Accardo S., Samanta E., Cimmino M. A., Giusti M., Monachesi M., Lomeo A. Preliminary results of serum androgen level testing in men with rheumatoid arthritis. Arthritis Rheum. 1984 Aug;27(8):958–959. doi: 10.1002/art.1780270821. [DOI] [PubMed] [Google Scholar]
  6. Cutolo M., Balleari E., Giusti M., Monachesi M., Accardo S. Sex hormone status in women suffering from rheumatoid arthritis. J Rheumatol. 1986 Dec;13(6):1019–1023. [PubMed] [Google Scholar]
  7. Emery A. E., Lawrence J. S. Genetics of ankylosing spondylitis. J Med Genet. 1967 Dec;4(4):239–244. doi: 10.1136/jmg.4.4.239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gerencer M., Tajić M., Kerhin-Brkljacić V., Kastelan A. An association between serum testosterone level and HLA phenotype. Immunol Lett. 1982 Mar;4(3):155–158. doi: 10.1016/0165-2478(82)90028-1. [DOI] [PubMed] [Google Scholar]
  9. Gordon D., Beastall G. H., Thomson J. A., Sturrock R. D. Androgenic status and sexual function in males with rheumatoid arthritis and ankylosing spondylitis. Q J Med. 1986 Jul;60(231):671–679. [PubMed] [Google Scholar]
  10. HERSH A. H., STECHER R. M., SOLOMON W. M., WOLPAW R., HAUSER H. Heredity in ankylosing spondylitis; a study of fifty families. Am J Hum Genet. 1950 Dec;2(4):391–408. [PMC free article] [PubMed] [Google Scholar]
  11. Hochberg M. C., Bias W. B., Arnett F. C., Jr Family studies in HLA-B27 associated arthritis. Medicine (Baltimore) 1978 Sep;57(5):463–475. doi: 10.1097/00005792-197809000-00005. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. James W. H. Parental hormone levels and mammalian sex ratios at birth. J Theor Biol. 1989 Jul 10;139(1):59–67. doi: 10.1016/s0022-5193(89)80057-8. [DOI] [PubMed] [Google Scholar]
  14. James W. H. The human sex ratio. Part 2: A hypothesis and a program of research. Hum Biol. 1987 Dec;59(6):873–900. [PubMed] [Google Scholar]
  15. James W. H. The hypothesized hormonal control of human sex ratio at birth--an update. J Theor Biol. 1990 Apr 23;143(4):555–564. doi: 10.1016/s0022-5193(05)80029-3. [DOI] [PubMed] [Google Scholar]
  16. KARTEN I., DITATA D., McEWEN C., TANNER M. A family study of rheumatoid (ankylosing) spondylitis. Arthritis Rheum. 1962 Apr;5:131–143. doi: 10.1002/art.1780050202. [DOI] [PubMed] [Google Scholar]
  17. Kousa M., Lassus A., Karvonen J., Tillikainen A., Aho K. Family study of Reiter's disease and HLA B27 distribution. J Rheumatol. 1977 Spring;4(1):95–102. [PubMed] [Google Scholar]
  18. Kuberski T. T. Ankylosing spondylitis associated with Trichomonas vaginalis infection. J Clin Microbiol. 1981 May;13(5):880–881. doi: 10.1128/jcm.13.5.880-881.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Lindberg H. Prevalence of primary coxarthrosis in siblings of patients with primary coxarthrosis. Clin Orthop Relat Res. 1986 Feb;(203):273–275. [PubMed] [Google Scholar]
  20. Lykken D. T., McGue M., Tellegen A. Recruitment bias in twin research: the rule of two-thirds reconsidered. Behav Genet. 1987 Jul;17(4):343–362. doi: 10.1007/BF01068136. [DOI] [PubMed] [Google Scholar]
  21. Meikle A. W., Bishop D. T., Stringham J. D., West D. W. Quantitating genetic and nongenetic factors that determine plasma sex steroid variation in normal male twins. Metabolism. 1986 Dec;35(12):1090–1095. doi: 10.1016/0026-0495(86)90020-x. [DOI] [PubMed] [Google Scholar]
  22. O'CONNELL D. Heredity in ankylosing spondylitis. Ann Intern Med. 1959 May;50(5):1115–1121. doi: 10.7326/0003-4819-50-5-1115. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Renard C., Vaiman M. Possible relationships between SLA and porcine reproduction. Reprod Nutr Dev. 1989;29(5):569–576. doi: 10.1051/rnd:19890506. [DOI] [PubMed] [Google Scholar]
  25. Rotter J. I., Wong F. L., Lifrak E. T., Parker L. N. A genetic component to the variation of dehydroepiandrosterone sulfate. Metabolism. 1985 Aug;34(8):731–736. doi: 10.1016/0026-0495(85)90023-x. [DOI] [PubMed] [Google Scholar]
  26. STECHER R. M., HERSH A. H. Familial occurrence of ankylosing spondylitis. Br J Phys Med. 1955 Aug;18(8):176–183. [PubMed] [Google Scholar]
  27. Silman A. J., Roman E., Beral V., Brown A. Adverse reproductive outcomes in women who subsequently develop rheumatoid arthritis. Ann Rheum Dis. 1988 Dec;47(12):979–981. doi: 10.1136/ard.47.12.979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Spector T. D., Ollier W. E., Perry L. A., Silman A. J. Evidence for similarity in testosterone levels in haplotype identical brothers. Dis Markers. 1988 Jun;6(2):119–125. [PubMed] [Google Scholar]
  29. Spector T. D., Perry L. A., Tubb G., Huskisson E. C. Androgen status of females with RA. Br J Rheumatol. 1987 Aug;26(4):316–318. doi: 10.1093/rheumatology/26.4.316. [DOI] [PubMed] [Google Scholar]
  30. Van Kerckhove C., Balakrishnan K., Levinson J. E., Larson M. G., Glass D. N. HLA and altered sex ratios in juvenile rheumatoid arthritis sibships. Hum Immunol. 1988 Aug;22(4):227–233. doi: 10.1016/0198-8859(88)90002-x. [DOI] [PubMed] [Google Scholar]
  31. de BLECOURT J., POLMAN A., de BLECOURT-MEINDERSMA Hereditary factors in rheumatoid arthritis and ankylosing spondylitis. Ann Rheum Dis. 1961 Sep;20:215–220. doi: 10.1136/ard.20.3.215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. de Groen P. C., Vukov L. F. Sexual intercourse: you, me, and the microbe makes three. JAMA. 1987 Oct 2;258(13):1730–1730. [PubMed] [Google Scholar]

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