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Leprosy is caused by Mycobacterium leprae and affects about 700,000 individuals each year. It has long been thought that leprosy has a strong genetic component, and recently we mapped a leprosy susceptibility locus to chromosome 6 region q25-q26 (ref. 3). Here we investigate this region further by using a systematic association scan of the chromosomal interval most likely to harbour this leprosy susceptibility locus. In 197 Vietnamese families we found a significant association between leprosy and 17 markers located in a block of approx. 80?kilobases overlapping the 5' regulatory region shared by the Parkinson's disease gene PARK2 and the co-regulated gene PACRG. Possession of as few as two of the 17 risk alleles was highly predictive of leprosy. This was confirmed in a sample of 975 unrelated leprosy cases and controls from Brazil in whom the same alleles were strongly associated with leprosy. Variants in the regulatory region shared by PARK2 and PACRG therefore act as common risk factors for leprosy. [ABSTRACT FROM AUTHOR]

Leprosy, a chronic infectious disease caused by Mycobacterium leprae, affects an estimated 700,000 persons each year. Clinically, leprosy can be categorized as paucibacillary or multibacillary disease. These clinical forms develop in persons that are intrinsically susceptible to leprosy per se, that is, leprosy independent of its specific clinical manifestation. We report here on a genome-wide search for loci controlling susceptibility to leprosy per se in a panel of 86 families including 205 siblings affected with leprosy from Southern Vietnam. Using model-free linkage analysis, we found significant evidence for a susceptibility gene on chromosome region 6q25 (maximum likelihood binomial (MLB) Iod score 4.31; P = 5 × 10[sup -6]). We confirmed this by family-based association analysis in an independent panel of 208 Vietnamese leprosy simplex families. Of seven microsatellite markers underlying the linkage peak, alleles of two markers (D651035 and D65305) showed strong evidence for association with leprosy (P = 6.7 × 10[sup -4] and P = 5.9 × 10[sup -5], respectively). [ABSTRACT FROM AUTHOR]

Analyzes the linkage between granulomatous reaction of lepromin and human NRAMP1 gene to intradermal injection in leprosy in Vietnam. Causes of haplotype sharing in the genome; Inducers of granuloma formation; Genetic factors involve in the regulation of Th1/Th2 balance in response to foreign antigens.

A genomewide association study in Chinese patients with leprosy detected association signals in 16 single-nucleotide polymorphisms (SNPs) belonging to 6 loci, of which 4 are related to the NOD2 signaling pathway and are Crohn's disease susceptibility loci. Here, we studied these 16 SNPs as potential leprosy susceptibility factors in 474 Vietnamese leprosy simplex families. We replicated SNPs at HLA-DR-DQ, RIPK2, CCDC122-LACC1, and NOD2 as leprosy susceptibility factors in Vietnam. These results validated the striking overlap in the genetic control of Crohn's disease and leprosy.

Background: Leprosy is a chronic infectious disease caused by Mycobacterium leprae. The Mitsuda reaction is a delayed granulomatous skin reaction elicited by intradermal injection of heat-killed M. leprae. Interestingly, results of the Mitsuda test are positive in the majority of individuals, even in areas not endemic for M. leprae. Like leprosy, the Mitsuda reaction is thought to be genetically controlled, but its mode of inheritance is unknown, although the role of the NRAMP1 gene has previously been reported., Methods: We conducted a segregation analysis of quantitative Mitsuda reactivity in 168 Vietnamese nuclear families ascertained through patients with leprosy., Results: We found strong evidence (P<10-9) for a major gene controlling the Mitsuda reaction independently of leprosy clinical status. Subsequent linkage analysis showed that this major gene was distinct from NRAMP1. Under the major-gene model, approximately 12% of individuals are homozygous for the recessive predisposing allele and are predicted to display high levels of Mitsuda reactivity (mean, approximately 10 mm, versus 5 mm in other individuals)., Conclusion: We provide evidence that the Mitsuda reaction is controlled by a major gene. Our study paves the way for the identification of this gene and should provide novel insight into the mechanisms involved in granuloma formation, especially in M. leprae infection.