02269nas a2200253   4500000000100000008004100001260001300042653002000055653003800075653001800113653003400131653001100165653001200176653002500188100001300213700001800226700001100244700001200255245003400267300001200301490000700313520168100320022001402001       2010                            d  c2010 Dec10aGenetic Linkage10aGenetic Predisposition to Disease10aGenome, Human10aGenome-Wide Association Study10aHumans10aleprosy10aMycobacterium leprae1 aMisch EA1 aBerrington WR1 aVary J1 aHawn TR00aLeprosy and the human genome.  a589-6200 v743 a<p>Despite the availability of effective treatment for several decades, leprosy remains an important medical problem in many regions of the world. Infection with Mycobacterium leprae can produce paucibacillary disease, characterized by well-formed granulomas and a Th1 T-cell response, or multibacillary disease, characterized by poorly organized cellular infiltrates and Th2 cytokines. These diametric immune responses confer states of relative resistance or susceptibility to leprosy, respectively, and have well-defined clinical manifestations. As a result, leprosy provides a unique opportunity to dissect the genetic basis of human in vivo immunity. A series of studies over the past 40 years suggests that host genes influence the risk of leprosy acquisition and the predilection for different clinical forms of the disease. However, a comprehensive, cellular, and molecular view of the genes and variants involved is still being assembled. In this article, we review several decades of human genetic studies of leprosy, including a number of recent investigations. We emphasize genetic analyses that are validated by the replication of the same phenotype in independent studies or supported by functional experiments demonstrating biological mechanisms of action for specific polymorphisms. Identifying and functionally exploring the genetic and immunological factors that underlie human susceptibility to leprosy have yielded important insights into M. leprae pathogenesis and are likely to advance our understanding of the immune response to other pathogenic mycobacteria. This knowledge may inform new treatment or vaccine strategies for leprosy or tuberculosis.</p>  a1098-5557