RESUMO
BACKGROUND: A genetic component to the etiology of leprosy is well recognized but the mechanism of inheritance and the genes involved are yet to be fully established. METHODOLOGY: A genome-wide single nucleotide polymorphism (SNP) based linkage analysis was carried out using 23 pedigrees, each with 3 to 7 family members affected by leprosy. Multipoint parametric and non-parametric linkage analyses were performed using MERLIN 1.1.1. PRINCIPAL FINDINGS: Genome-wide significant evidence for linkage was identified on chromosome 2p14 with a heterogeneity logarithm of odds (HLOD) score of 3.51 (rs1106577) under a recessive model of inheritance, while suggestive evidence was identified on chr.4q22 (HLOD 2.92, rs1349350, dominant model), chr. 8q24 (HLOD 2.74, rs1618523, recessive model) and chr.16q24 (HLOD 1.93, rs276990 dominant model). Our study also provided moderate evidence for a linkage locus on chromosome 6q24-26 by non-parametric linkage analysis (rs6570858, LOD 1.54, pâ=â0.004), overlapping a previously reported linkage region on chromosome 6q25-26. CONCLUSION: A genome-wide linkage analysis has identified a new linkage locus on chromosome 2p14 for leprosy in Pedigrees from China.
Assuntos
Cromossomos Humanos Par 2/genética , Predisposição Genética para Doença , Hanseníase/genética , Povo Asiático/genética , Cromossomos Humanos , Família , Feminino , Ligação Genética , Estudo de Associação Genômica Ampla , Humanos , Escore Lod , Masculino , Linhagem , Polimorfismo de Nucleotídeo ÚnicoRESUMO
The Mitsuda reaction, a delayed granulomatous skin reaction elicited by the intradermal injection of heat-killed Mycobacterium leprae, is an in vivo test reflecting the ability to generate an immune granuloma after sensitization by diverse mycobacterial infections. Accumulating evidence for the genetic control of the Mitsuda reaction has been reported. We performed a genomewide linkage scan for the quantitative Mitsuda reaction in 19 large families from Vietnam with a history of leprosy (114 offspring). Suggestive linkage was found at chromosomal regions 2q35 (P = 9 x 10(-4) at the SLC11A1 locus) and 17q21-25 (P = 8 x 10(-4)). Interestingly, these 2 regions have been previously linked to mycobacterial infection and other granulomatous diseases.
Assuntos
Proteínas de Transporte de Cátions/genética , Predisposição Genética para Doença/genética , Granuloma/genética , Hanseníase/genética , Mycobacterium leprae/imunologia , Cromossomos Humanos Par 17/genética , Cromossomos Humanos Par 2/genética , Ligação Genética , Granuloma/imunologia , Granuloma/microbiologia , Humanos , Hanseníase/imunologia , Mycobacterium leprae/patogenicidade , VietnãRESUMO
Two genetic loci, viz. COL3A and CTLA4, located within the chromosome 2q31-33 region in the vicinity of the proposed syntenic site of the mouse "Bcg" locus were genotyped by the polymerase chain reaction in leprosy patients and healthy individuals. All the subjects studied were assessed as in-vitro responders/non-responders to mycobacterial antigens. Simple sequence length polymorphism analysis revealed five (236 to 312 bp) and eight (84 to 120 bp) allelomorphs for COL3A and CTLA4, respectively. Our preliminary analysis showed a significant association between the 250-bp COL3A allelomorph in the homozygous condition and the multibacillary form of leprosy (P < 0.05: relative risk = 5.5). Another allelic (312 bp) variant of COL3A was significantly correlated with non-responsiveness to M. leprae antigens in vitro (P < 0.01). The 104-bp allelomorph of CTLA4 was not observed in any of the 25 cases of leprosy. This absence was statistically significant (P < 0.05) when compared with normal healthy controls and depicted a high relative risk (RR = 25.83). An additional observation of the predominance of a unique 84-bp CTLA4/CTLA4-like allelomorph was observed in the Indian subjects studied.