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, Betty P. Tsao, Ph.D., a professor of medicine in the Division of Rheumatology at the David Geffen School of Medicine at UCLA, and colleagues 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 study was funded by the Lupus Research Institute, a nonprofit association dedicated to supporting innovative research in lupus.
The research appears in the Aug. 23 online edition of the journal Proceedings of the National Academy of Sciences (PNAS).
- Nan Shen, Qiong Fu, Yun Deng, Xiaoxia Qian, Jian Zhao, Kenneth M. Kaufman, Yee Ling Wu, C. Yung Yu, Yuanjia Tang, Ji-Yih Chen, Wanling Yang, Maida Wong, Aya Kawasaki, Naoyuki Tsuchiya, Takayuki Sumida, Yasushi Kawaguchi, Hwee Siew Howe, Mo Yin Mok, So-Young Bang, Fei-Lan Liu, Deh-Ming Chang, Yoshinari Takasaki, Hiroshi Hashimoto, John B. Harley, Joel M. Guthridge, Jennifer M. Grossman, Rita M. Cantor, Yeong Wook Song, Sang-Cheol Bae, Shunle Chen, Bevra H. Hahn, Yu Lung Lau, and Betty P. Tsao. Sex-specific association of X-linked Toll-like receptor 7 (TLR7) with male systemic lupus erythematosus. Proceedings of the National Academy of Sciences, 2010; DOI: 10.1073/pnas.1001337107
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