Major Finding on the Development of Male Lupus
Dr. Tsao's discovery that the lupus link to TLR7 is stronger in males supports the idea that there are different genetic pathways to lupus between males and females. Only 10 percent of people with lupus are male, but the disease tends to be particularly severe in this population.
In her novel study, Dr. Tsao and colleagues noted that men with an extra X (female) chromosome have a higher risk for lupus, and predicted that genes located on the X chromosome would be critical in male lupus. So they narrowed their search among the approximately 2,000 genes on the X chromosome to genes already implicated in lupus.
After genotyping DNA of blood samples from over 4,000 people with lupus from East Asia, the team discovered a variant form of the TLR7 gene associated with lupus. The link was stronger in men of Chinese and Japanese ethnicity89% of men with lupus had the risk allele, compared with only 77% of healthy male subjects.
"Now that we know the sex-specific genetic contributions to lupus, we can proceed to find more targeted therapies than currently exist," said Dr. Tsao.
Lupus Research Institute Successfully Pioneers Discovery
It was nearly a decade ago that the LRI supported a bold and innovative hypothesis that Dr. Tsao subsequently built uponthat a strain of mice prone to lupus carry an extra copy of the TLR7 gene located on the Y-chromosome. Silvia Bolland, PhD, made this major discovery soon after she joined the NIH to form her own group.
The LRI subsequently supported Dr. Tsao's innovative proposal to translate Dr. Bolland's discovery in mice to a discovery in humans.
|Contact: Liz Bryan|
Lupus Research Institute