The application of this approach to a family-based association study of leprosy susceptibility successfully refined the association signal at two candidate loci, C1orf141-IL23R on chromosome 1 and RAB32-C6orf103 on chromosome 6.
Copy number variation analysis showed an increased copy number of the IL23R gene (PB=36.4%, controls=20.2%; p=0.026) associated with the pauci-bacillary form of leprosy, which correlated with a trend towards enhanced expression in memory T cells in a preliminary observation.
The IL23R association supports previous observations of the marked overlap of susceptibility genes for leprosy and Crohn's disease, implying common pathogenesis mechanisms.
The application of this approach to a family-based association study of leprosy susceptibility successfully refined the association signal at two candidate loci, C1orf141-IL23R on chromosome 1 and RAB32-C6orf103 on chromosome 6.
In addition to identifying LTA as a major gene associated with early-onset leprosy, our study highlights the critical role of case- and population-specific factors in the dissection of susceptibility variants in complex diseases.
Besides confirming all previously published loci, we discovered six new susceptibility loci, and further gene prioritization analysis of these loci implicated BATF3, CCDC88B and CIITA-SOCS1 as new susceptibility genes for leprosy.
We have conducted an association analysis of more than 1,500 individuals from different case-control and family studies, and observed consistent associations between genetic variants in both TLR1 and the HLA-DRB1/DQA1 regions with susceptibility to leprosy (TLR1 I602S, case-control P = 5.7 x 10(-8), OR = 0.31, 95% CI = 0.20-0.48, and HLA-DQA1 rs1071630, case-control P = 4.9 x 10(-14), OR = 0.43, 95% CI = 0.35-0.54).
These data confirm the positive association of HLA-DR2 (DRB1*16) with leprosy per se, and the protector effect of DRB1*04 against lepromatous leprosy in Brazilian patients.
The frequency of HLA-DRB1* alleles between the control group and leprosy patient subgroups presenting different forms of the disease showed that the HLA-DRB1*16 (16.13% vs. 8.24%, OR = 4.10, CI = 1.27-13.27, p = 0.010) and HLA-DRB1*14 (5% vs. 3.53%, OR = 4.63, CI = 1.00-21.08, p = 0.032) alleles were significantly more frequent in patients with different clinical subtypes of leprosy.
The aim of this study was to investigate whether single nucleotide polymorphisms in NOD2, C13orf31, and CCDC122 genes are associated with leprosy among the Chinese Yi population in China.
Genetic variation in the Laccase (multicopper oxidoreductase) domain-containing 1 (LACC1) gene has been shown to affect the risk of Crohn's disease, leprosy and, more recently, ulcerative colitis and juvenile idiopathic arthritis.
The associations with MICA and MICB cannot be accounted for by linkage disequilibrium with the HLA class II locus indicating a role in genetic susceptibility to leprosy that is independent of HLA-DRB1.
Consistently, mRNA expression levels of both HIF1A and LACC1 were upregulated in the skin lesions of individuals with leprosy and in Mycobacterium leprae-stimulated cells, indicating an active role of HIF1A and LACC1 in leprosy pathogenesis.
Both common and rare genetic variants of laccase domain-containing 1 (<i>LACC1</i>, previously C13orf31) are associated with inflammatory bowel disease, leprosy, Behcet disease, and systemic juvenile idiopathic arthritis.
Single-nucleotide variations in C13orf31 (LACC1) that encode p.C284R and p.I254V in a protein of unknown function (called 'FAMIN' here) are associated with increased risk for systemic juvenile idiopathic arthritis, leprosy and Crohn's disease.
The function of the Laccase domain-containing 1 (LACC1) gene is unknown, but genetic variation at this locus has been reported to consistently affect the risk of Crohn's disease (CD) and leprosy.
The much stronger association of DRB1*1501 with the multibacillary form than with the TT type of leprosy suggests a possible role in the differential immune response to M. leprae antigens.
The HLA-DRB1 alleles could act alone or in combination with other genes to confer differential susceptibility and also protection to leprosy disease in endemic areas of the American continent.
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=194 families).