02086nas a2200313   4500000000100000008004100001653002600042653001200068653002100080653001700101653001500118100001300133700001200146700001500158700001700173700001800190700001500208700001100223700001300234700001200247700001300259700001300272700001100285700001300296700001300309245010700322520132900429022001401758       2014                            d10aInflammatory response10aleprosy10aType 1 reactions10aNerve damage10aDisability1 aFava V M1 aCobat A1 aVan Thuc N1 aLatini A C P1 aStefani M M A1 aBelone A F1 aBa N N1 aOrlova M1 aManry J1 aMira M T1 aThai V H1 aAbel L1 aAlcais A1 aSchurr E00aTNFSF8 regulatory variants are associated with excessive inflammatory responses but not leprosy per se3 aBackground
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.   a0022-1899