Discovery of four exonic and one intergenic novel susceptibility loci for leprosy.

Discovery of four exonic and one intergenic novel susceptibility loci for leprosy.
Clin Genet. 2018 May 03;:
Authors: Wang Z, Mi Z, Wang H, Sun L, Yu G, Fu X', Wang C, Bao F, Yue Z, Zhao Q, Wang N, Cheng X, Liu H, Zhang F
Abstract
Seven new risk coding variants have been identified through an exome-wide association study (EWAS), which studied the contributions of protein-coding variants to leprosy susceptibility. But some potential susceptibility loci were not studied in the previous EWAS study because of the project consideration. Seventeen unstudied potential susceptibility loci of the previous EWAS were validated in 3,169 cases and 9,814 controls in this study. Four disease associated exonic loci were identified: rs671 in ALDH2 (P = 2.0 × 10-20 , odds ratio (OR) = 1.35), rs13259978 in SLC7A2 (P = 1.74 × 10-8 , OR = 1.28), rs925368 in GIT2 (P = 9.18 × 10-17 , OR = 1.44), and rs75680863 in TCN2 (P = 8.37 × 10-21 , OR = 0.74). Potentially implicating ZFP36L1 as a new susceptibility gene, one intergenic SNP, rs1465788 (P = 7.81 × 10-6 , OR = 0.88), was also suggested to be associated with leprosy. A luciferase reporter assay showed that the rs1465788 risk allele notably decreased the transcription activity of the flanking sequence. These findings suggest the possible involvement of lipid metabolism, NF-κB homeostasis and macrophage antimicrobial pathways in leprosy pathogenesis.
PMID: 29722023 [PubMed - as supplied by pu...

Source: Clinical Genetics - May 3, 2018 Category: Genetics & Stem Cells Authors: Wang Z, Mi Z, Wang H, Sun L, Yu G, Fu X', Wang C, Bao F, Yue Z, Zhao Q, Wang N, Cheng X, Liu H, Zhang F Tags: Clin Genet Source Type: research