HLA-DR-associated genetic control of the type of leprosy in a population from Surinam

Eden, Willem van; Vries, RenéR.P. de; D’Amaro, J.; Schreuder, Ieke; Leiker, D. L.; Rood, Jon J. van

doi:10.1016/0198-8859(82)90007-6

Cited by 69 publications

(26 citation statements)

References 25 publications

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“…Further investigation of the Vietnamese population 16 indicates linkage to clinical sub-type, as many earlier studies (e.g. 17,18 ) had suggested. Overall, a complex picture of geographic heterogeneity in genetic effects on these different mycobacterial infections is emerging.…”

Section: à7mentioning

confidence: 89%

“…As outlined in the legend to Table 2, nonparametric linkage analysis in ALLEGRO 12 that reports maximum Z scores for the likelihood ratio (Z lr ) and allele-sharing LOD scores 13 was used to analyse the genome scan linkage data. This analysis provided evidence at Po0.05 for linkage of susceptibility to 8 regions of the genome on chromosomes 2, 3, 7, 10, 11, 20, 21 and X (LOD scores 0.60 to 2.43; 1-sided p values 0.0004oPo0.048) for tuberculosis, and to 9 regions on chromosomes 6,9,11,12,13,15,16,17,20 (LOD scores 0.74 to 2.50; 1-sided P values 0.0003oPo0.033) for leprosy per se. For tuberculosis, 58 markers from the positive regions were typed in a second set of families (Table 1), with 22 additional markers typed in both family sets.…”

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confidence: 99%

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Genome-wide scans for leprosy and tuberculosis susceptibility genes in Brazilians

et al. 2004

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Genome-wide scans were conducted for tuberculosis and leprosy per se in Brazil. At stage 1, 405 markers (10 cM map) were typed in 16 (178 individuals) tuberculosis and 21 (173 individuals) leprosy families. Nonparametric multipoint analysis detected 8 and 9 chromosomal regions respectively with provisional evidence (Po0.05) for linkage. At stage 2, 58 markers from positive regions were typed in a second set of 22 (176 individuals ; D17S1868, 2.38, P¼0.0005; D20S889, 1.51, P¼0.004). The peak at D20S889 for leprosy is 3.5 Mb distal to that reported at D20S115 for leprosy in India. (151 words).

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Section: à7mentioning

confidence: 89%

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confidence: 99%

Genome-wide scans for leprosy and tuberculosis susceptibility genes in Brazilians

et al. 2004

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“…HLA-DR3 was associated with tuberculoid leprosy in Mexico 34 and in the South American populations of Surinam 35 and Venezuela, 10 whereas it was found at lower frequencies in lepromatous patients. 35,36 T-cell proliferation responses to certain epitopes of the mycobacterial hsp65 (p3-13) are DR3 restricted 37 and DR3 was associated with low T-cell responses to M. leprae in tuberculoid patients.…”

Section: Class II Regionmentioning

confidence: 92%

Genetics of susceptibility to leprosy

2002

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The ancient disease of leprosy can cause severe disability and disfigurement and is still a major health concern in many parts of the world. Only a subset of those individuals exposed to the pathogen will go on to develop clinical disease and there is a broad clinical spectrum amongst leprosy sufferers. The outcome of infection is in part due to host genes that influence control of the initial infection and the host's immune response to that infection. Identification of the host genes that influence host susceptibility/resistance will enable a greater understanding of disease pathogenesis. In turn, this should facilitate development of more effective therapeutics and vaccines. So far at least a dozen genes have been implicated in leprosy susceptibility and a genome-wide linkage study has lead to the identification of at least one positional candidate. These findings are reviewed here.

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“…In addition, HLA-DR3 has been found associated with leprosy susceptibility in Surinam and Mexico. 18,19 Some of these studies had limited power owing to low numbers of individuals recruited. Moreover, to avoid premature conclusions, independent replication studies with different populations for confirmation of previous findings are necessary in multifactorial diseases, such as leprosy.…”

Section: Introductionmentioning

confidence: 99%

HLA-DRB104 and DRB110 are associated with resistance and susceptibility, respectively, in Brazilian and Vietnamese leprosy patients

et al. 2007

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The host genetic background has been considered one of the factors that influence leprosy outcome, a chronic infectious disease caused by Mycobacterium leprae. Genome scans demonstrated that the 6p21 region is associated with leprosy and a substantial number of population-based studies analyzing human leukocyte antigen (HLA) class II loci suggested association of HLA-DR with leprosy. However, some studies lacked robustness as they had limited power. Indeed, experimental designs require increased sample size to achieve adequate power, as well as replication studies with independent samples for confirmation of previous findings. In this work, we analyzed the influence of the HLA-DRB1 locus on leprosy susceptibility per se and disease type using a case-control design carried out in Brazilians (578 cases and 691 controls) and a replication study based on a family design in a Vietnamese population (n ¼ 194 families). The results showed that HLA-DRB1*10 is associated with susceptibility to leprosy and HLA-DRB1*04 is associated with resistance, both in the Brazilian and Vietnamese populations suggesting that these alleles play an important role in the activation of cellular immune responses against M. leprae.

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HLA-DR-associated genetic control of the type of leprosy in a population from Surinam

Cited by 69 publications

References 25 publications

Genome-wide scans for leprosy and tuberculosis susceptibility genes in Brazilians

Genome-wide scans for leprosy and tuberculosis susceptibility genes in Brazilians

Genetics of susceptibility to leprosy

HLA-DRB104 and DRB110 are associated with resistance and susceptibility, respectively, in Brazilian and Vietnamese leprosy patients

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HLA-DR-associated genetic control of the type of leprosy in a population from Surinam

Cited by 69 publications

References 25 publications

Genome-wide scans for leprosy and tuberculosis susceptibility genes in Brazilians

Genome-wide scans for leprosy and tuberculosis susceptibility genes in Brazilians

Genetics of susceptibility to leprosy

HLA-DRB1*04 and DRB1*10 are associated with resistance and susceptibility, respectively, in Brazilian and Vietnamese leprosy patients

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Product

Resources

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HLA-DRB104 and DRB110 are associated with resistance and susceptibility, respectively, in Brazilian and Vietnamese leprosy patients