165 Elucidating the METTL3-m6A epitranscriptome in epidermal development and carcinogenesis

Abstract

Responses to psoriasis treatment vary dramatically among patients. Pharmacogenetic studies seek to identify genetic variations that are associated with treatment response. In this study, we assessed the responses to nine treatment options (acitretin, adalimumab, coal tar, calcipotriol, dithranol, etanercept, methotrexate, photochemotherapy, and ultraviolet B radiation) among 1,692 patients that were genotyped in our recent GWAS. The number of patients administered for each treatment ranged from 127 to 1,182. Among these treatment options, the rate of self-reported treatment effectiveness had a wide range from 19.4% to 62.3%. For instance, the response rates for etanercept, adalimumab, and calcipotriol were 62.3%, 52.2%, and 19.4%, respectively. Associations between genetic markers (SNPs and INDELs) and self-reported treatment response were evaluated after adjusting for population stratification using principal components. In total, 6,502,658 common ( 5% minor allele frequency), well imputed (R 2 0.7), markers were included. We identified two loci achieving suggestive significance (p ¼ 5 x 10 -6 ) located in previously identified psoriasis-associated loci: 13q14.3 (p ¼ 2.6 x 10 -6 ) was associated with response to coal tar (978 patients), and 6p22.2 (p ¼ 3.4 x 10 -6 ) was associated with response to calcipotriol (1,182 patients). We further revealed that multiple markers in the 13q14.3 locus overlap with an active enhancer region (p ¼ 8.6 x 10 -5 ). This study provides support for the hypothesis that psoriasis-associated loci are also associated with treatment responses.