期刊
JOURNAL OF INFECTIOUS DISEASES
卷 211, 期 6, 页码 968-977出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiu566
关键词
leprosy; TNFSF8; TNFSF15; eQTL; Type 1 reaction
资金
- Canadian Institutes of Health Research
- l'Ordre de Malte (MALTALEP)
- L'Agence Nationale de la Recherche
- Ministry of Education of Brazil (Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior) [9074/11-2]
- Government of Canada
Background. Type 1 reactions (T1R) affect a considerable proportion of patients with leprosy. In those with T1R, the host immune response pathologically overcompensates for the actual infectious threat, resulting in nerve damage and permanent disability. Based on the results of a genome-wide association study of leprosy per se, we investigated the TNFSF15 chromosomal region for a possible contribution to susceptibility to T1R. Methods. We performed a high-resolution association scan of the TNFSF15 locus to evaluate the association with T1R in 2 geographically and ethnically distinct populations: a family-based sample from Vietnam and a case-control sample from Brazil, comprising a total of 1768 subjects. Results. In the Vietnamese sample, 47 single-nucleotide polymorphisms (SNPs) overlapping TNFSF15 and the adjacent TNFSF8 gene were associated with T1R but not with leprosy. Of the 47 SNPs, 39 were cis-expression quantitative trait loci (cis-eQTL) for TNFSF8 including SNPs located within the TNFSF15 gene. In the Brazilian sample, 18 of these cis-eQTL SNPs overlapping the TNFSF8 gene were validated for association with T1R. Conclusions. Taken together, these results indicate TNFSF8 and not TNFSF15 as an important T1R susceptibility gene. Our data support the need for infection genetics to go beyond genes for pathogen control to explore genes involved in a commensurate host response.
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