02540nas a2200433 4500000000100000008004100001260001600042653001100058653002100069653003800090653001500128653001100143653002800154653001300182653001200195653002500207653002500232653000900257653002500266653000900291653001200300100001300312700001400325700001500339700001400354700001200368700001300380700001000393700001200403700001300415700001100428245009000439856006700529300001200596490000800608050001600616520146000632022001402092 2005 d c2005 Oct 1510aFemale10aGenes, Recessive10aGenetic Predisposition to Disease10aHaplotypes10aHumans10aInjections, Intradermal10aLepromin10aleprosy10aLeprosy, lepromatous10aLeprosy, Tuberculoid10aMale10aMycobacterium leprae10aSkin10aVietnam1 aRanque B1 aAlcaïs A1 aVan Thuc N1 aWoynard S1 aThai VH1 aHuong NT1 aBa NN1 aKhoa PX1 aSchurr E1 aAbel L00aA recessive major gene controls the mitsuda reaction in a region endemic for leprosy. uhttp://jid.oxfordjournals.org/content/192/8/1475.full.pdf+html a1475-820 v192 aRANQUE 20053 a

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.

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