TY - JOUR
KW - Inflammatory response
KW - leprosy
KW - Type 1 reactions
KW - Nerve damage
KW - Disability
AU - Fava V M
AU - Cobat A
AU - Van Thuc N
AU - Latini A C P
AU - Stefani M M A
AU - Belone A F
AU - Ba N N
AU - Orlova M
AU - Manry J
AU - Mira M T
AU - Thai V H
AU - Abel L
AU - Alcais A
AU - Schurr E
AB - Background
Type-1 Reactions (T1R) affect a considerable proportion of leprosy patients. In T1R cases, 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 two 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 SNPs overlapping TNFSF15 and the adjacent TNFSF8 gene were associated with T1R but not with leprosy. Of the 47 SNPs, 39 were 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. 
BT - Journal of Infectious Diseases
DO - 10.1093/infdis/jiu566
LA - eng
N2 - Background
Type-1 Reactions (T1R) affect a considerable proportion of leprosy patients. In T1R cases, 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 two 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 SNPs overlapping TNFSF15 and the adjacent TNFSF8 gene were associated with T1R but not with leprosy. Of the 47 SNPs, 39 were 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. 
PY - 2014
T2 - Journal of Infectious Diseases
TI - TNFSF8 regulatory variants are associated with excessive inflammatory responses but not leprosy per se
SN - 0022-1899
ER -