Sex chromosome aneuploidies among men with systemic lupus erythematosus

• Published in: Journal of autoimmunity Vol. 38; no. 2; pp. J129 - J134
• Main Authors: Dillon, Skyler P, Kurien, Biji T, Li, Shibo, Bruner, Gail R, Kaufman, Kenneth M, Harley, John B, Gaffney, Patrick M, Wallace, Daniel J, Weisman, Michael H, Scofield, R. Hal
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-05-2012
• Subjects: Allergy and Immunology; Aneuploidy; Chromosomes, Human, X; Female bias; Glyceraldehyde 3-Phosphate Dehydrogenase (NADP+) - genetics; Humans; Klinefelter’s syndrome; Lupus Erythematosus, Systemic - genetics; Male; Male 46,XX; Polymorphism, Single Nucleotide; Receptors, Androgen - genetics; Sex Chromosome Aberrations; Sex Factors; Sex-Determining Region Y Protein - genetics; Systemic lupus erythematosus; X chromosome; Systemic lupus erythematosus; Klinefelter’s syndrome; Male 46,XX; Female bias; X chromosome
• ISSN: 0896-8411; 1095-9157
• DOI: 10.1016/j.jaut.2011.10.004

Abstract About 90% of patients with systemic lupus erythematosus (SLE) are female. We hypothesize that the number of X chromosomes, not sex, is a determinate of risk of SLE. Number of X chromosomes was determined by single nucleotide typing and then confirmed by karyotype or fluorescent in situ hybridization in a large group of men with SLE. Presence of an sry gene was assessed by RT-PCR. We calculated 96% confidence intervals using the Adjusted Wald method, and used Bayes’ theorem to estimate the prevalence of SLE among 47,XXY and 46,XX men. Among 316 men with SLE, 7 had 47,XXY and 1 had 46,XX. The rate of Klinefelter’s syndrome (47,XXY) was statistically different from that found in control men and from the known prevalence in the population. The 46,XX man had an sry gene, which encodes the testes determining factor, on an X chromosome as a result of an abnormal crossover during meiosis. In the case of 46,XX, 1 of 316 was statistically different from the known population prevalence of 1 in 20,000 live male births. A previously reported 46,XX man with SLE had a different molecular mechanism in which there were no common gene copy number abnormalities with our patient. Thus, men with SLE are enriched for conditions with additional X chromosomes. Especially since 46,XX men are generally normal males, except for infertility, these data suggest the number of X chromosomes, not phenotypic sex, is responsible for the sex-bias of SLE.