HLA-Linked Genes and Leprosy: A Family Study in Karigiri, South India

Abstract

The evidence for a genetic determination of susceptibility to leprosy is reviewed. To test the hypothesis that an HLA (histocompatibility leukocyte antigen)-linked gene is associated with such susceptibility, the association between the distribution of leprosy within a family and the segregation of HLA haplotypes was investigated among 72 families who lived in Karigiri, Tamil Nadu State, South India. A statistically significant association was found for families in which siblings had tuberculoid leprosy and in which neither parent had leprosy. The findings from the data of this study agree with those of two previous studies carried out among smaller populations is Surinam and Wardha, Maharashtra State, India. Such an agreement suggests that a genetic determinant which is linked to the major HLA locus on chromosome 6 and which is probably recessive affects susceptibility to tuberculoid leprosy in humans.

Segregation of HLA/TNF region is linked to leprosy clinical spectrum in families displaying mixed leprosy subtypes

“…However, when correcting the P-value for multiple testing and performing multipoint analysis, this result was no more significant. This negative finding is consistent with previous reports showing that HLA haplotypes segregated randomly among affected 25 and healthy 26 siblings in multicase leprosy families, suggesting that HLA has little effect on susceptibility to leprosy per se.…”

“…Clinical manifestations of leprosy have been associated or linked with the HLA/TNF region in multiple studies (reviewed by Meyer et al, 8 and Casanova and Abel 5 ). Non-random segregation of parental HLA haplotypes was observed among sets of children with TT leprosy from Surinam, 27 Central 27 and South 25 India, Venezuela 26 , and Egypt. 28 Similar results were obtained for siblings with LL leprosy from Venezuela 26 and China.…”

Genetics of susceptibility to leprosy

“…The HLA genes were one of the first class of genes to be implicated in susceptibility to leprosy, and there have been numerous studies in many populations, probably partly because their gene products were such a likely biological candidate (the main hypothesis being that presentation of certain antigens in a specific HLA context may influence the type of T-cell response that develops), and partly because serological typings could be performed in the pre-genotyping era. A series of family studies in various populations have shown non-random segregation of parental HLA haplotypes amongst tuberculoid children [7][8][9][10][11] and lepromatous children. 10,12 As HLA haplotypes segregated randomly among healthy siblings 8,10 it was suggested early on that genes in the MHC region might influence leprosy type rather than susceptibility to leprosy per se.…”

“…A series of family studies in various populations have shown non-random segregation of parental HLA haplotypes amongst tuberculoid children [7][8][9][10][11] and lepromatous children. 10,12 As HLA haplotypes segregated randomly among healthy siblings 8,10 it was suggested early on that genes in the MHC region might influence leprosy type rather than susceptibility to leprosy per se.…”

HLA-linked control of the course ofM. leprae infections

“…As far as we know 6 family studies were performed (23)(24)(25)(26)(27)(28) , of wh ich 3 by the same group , name ly ourselve s (23,25,27) .…”