Leprosy susceptibility - 7 genes identified

Seven genes that increase an individual's susceptibility to leprosy have been identified, report Asian scientists.

Discovered during the first genome-wide association study (GWAS) of leprosy by scientists at the Genome Institute of Singapore (GIS) and 26 institutes in China, the finding highlights the important role of the innate immune response in the development of leprosy.

"Though leprosy is not common, the discoveries have significant ramifications for chronic infectious disorders and for host-pathogen interactions in other more prevalent mycobacterial diseases such as tuberculosis," said Dr. Edison Liu, executive director of GIS, which is sponsored by Singapore's Agency for Science, Technology and Research (A*STAR).

Dr. Tom H.M. Ottenhoff (Ph.D), professor in immunology, Leiden University Medical Center, The Netherlands, said, "This is a very impressive study, which uncovers entirely new genes that control susceptibility to leprosy and, perhaps, other related diseases. A great asset is that the study underpins the genetic data with plausible functional biology experimentation, which is not often seen."

The scientists analyzed over 10,000 samples from leprosy patients and health controls in China, and discovered seven genes associated with susceptibility to leprosy: CCDC122, C13orf31, NOD2, TNFSF15, HLA-DR, RIPK2 and LRRK2. [N Engl J Med 2009 Dec 16; Epub ahead of print]

According to Jianjun Liu (Ph.D), human genetics group leader at GIS, the findings are significant and could only be achieved through large-scale genetic studies done in close collaboration with multi-disciplinary research groups across different countries.

The study, added the executive director of GIS, is a continuation of several deep, collaborative studies between GIS and Chinese scientists in using population sciences to uncover genetic modifiers of human disease.

"The key to this collaboration and one that was recently published on the genetics of Asian migration is that the studies were initiated and executed by Asian partners acting as equals. Hopefully, this will initiate a new phase of cooperation between historically competing Asian countries whose primary links have been with western communities."

Leprosy, a chronic infectious disease caused by Mycobacterium leprae, mainly affects skin and peripheral nerves, and may lead to irreversible disabilities. Although largely eliminated in developed countries, leprosy is still a major public health problem in many developing nations, particularly in tropic and sub-tropic regions. Although many people are potentially exposed to M. leprae in endemic regions, only a small minority will be infected and develop clinically overt leprosy, suggesting that only some individuals are susceptible to this disease.

Because M. leprae cannot be cultured in the laboratory, and as it only infects humans and armadillos, research and, thus, the biological understanding of leprosy is very limited. The discovery of the seven genes not only improves scientific understanding about genetic susceptibility to the disease, but may also stimulate additional biological and clinical research to reveal the mechanism of leprosy development.