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

Abstract

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).

Interleukin-10 promoter single-nucleotide polymorphisms as markers for disease susceptibility and disease severity in leprosy

“…Recent findings have defined other genomic regions (6q25 and 17q11À21) associated with leprosy susceptibility. 5,6,21 The À3575A/À2849G/À2763C or À3575T/À2849A/ À2763C haplotype is a minor haplotype in the different populations studied, 11,12 and occurs at relatively low frequencies among patients and controls also among Brazilians and Dutch. 17 This suggests that its overall contribution to disease resistance at the population level is limited, which means that the results need replication in other populations to confirm the findings.…”

“…As mentioned earlier, only a small proportion of the leprosy patients possess the IL-10 haplotypes associated with disease or disease severity, and some patients still carry the leprosy resistance-associated haplotype, indicating that the outcome of mycobacterial disease is due to complex interactions between several host genes, likely including other cytokine genes and receptors, HLA-encoded genes (including TNF-a) and others. 2,5,6,21 Furthermore, it cannot be excluded that the genetic control of susceptibility to leprosy is heterogeneous such that different loci could control the same phenotype. Our Haplotype score tests were calculated using the posterior probability of an individual having a haplotype, given the genotype, in the context of generalized linear models.…”

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

“…5,6 Two recent genome scans have pinpointed chromosome 6p21 as a leprosy susceptibility locus. 7,8 This region harbors the HLA gene cluster, which has been extensively studied for its role in leprosy pathogenesis. [9][10][11][12] Candidate gene studies have detected association of leprosy with both class I and II genes.…”

Genome-wide SNP-based linkage analysis of tuberculosis in Thais

“…The 20p region is of particular interest for tuberculosis susceptibility because it has been shown to have significant evidence of linkage with leprosy. 15,30 The susceptibility gene(s) in this region may play a role in susceptibility to primary tuberculosis in pediatric and adolescent cases. Several promising candidate genes in this region are a cluster of b-defensin genes that play important roles in innate immunity against respiratory infection.…”

“…10,13 Suggestive evidence of linkage was also found on chromosomes 10q26, 11q12 and 20p12 in the Brazilian population. 14,15 The only significant linkage evidence (logarithm of odds (LOD) ¼ 3.49) to date is a study of 96 Moroccan multiplex families that implicated an autosomal-dominant gene on chromosome 8q12-q13. 16 Distribution of virulent M. tuberculosis strains such as Beijing strain differs among regions of the world, 17 which suggests its adaptation to different human populations.…”