Genes reside along long chains of DNA called chromosomes. UCLA researchers have found that a variation in a gene on the sex chromosome X may enhance an immune response that leads to lupus in men.
Systemic lupus erythematosus (SLE) is an autoimmune disease that predominantly affects women. Interestingly, researchers found that although the variation occurred in a gene on the X, or female, chromosome, its influence was stronger in men than in women. Humans hold two sex chromosomes — men have an X and Y, while women have two Xs. Previous studies have shown that genetic variations on the X chromosome contribute to the development of lupus.
In this study, researchers found that certain common variations of DNA sequences within a specific X-linked gene triggered a stronger response in the immune system, increasing the risk of developing lupus, especially in men.
This study was part of an international effort to study the genetics of lupus in broader ethnic groups. Researchers genotyped 9,274 Eastern Asians individuals, including those with lupus and healthy controls. The stronger genetic effects were seen in men, compared with women, and especially in Chinese and Japanese men. Further study will look at other ethnicities.
Researchers say the finding will lead to greater understanding of the development of lupus and to further exploration of the sex-specific genetic contributions of the disease, which could result in more targeted therapies.
The research appears in the Aug. 23 online edition of the journal Proceedings of the National Academy of Sciences (PNAS).