AUTHOR=Ren Yunqing , Wang Ling , Dai Huatuo , Qiu Guiying , Liu Jipeng , Yu Dianhe , Liu Jianjun , Lyu Cheng-Zhi , Liu Lunfei , Zheng Min TITLE=Genome-wide association analysis of anti-TNF-α treatment response in Chinese patients with psoriasis JOURNAL=Frontiers in Pharmacology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.968935 DOI=10.3389/fphar.2022.968935 ISSN=1663-9812 ABSTRACT=

Background: TNF-α inhibitors are effective biological agents for treating psoriasis, but the treatment responses differ across patients. This study aimed to identify genetic biomarkers of anti-TNF-α response in Chinese psoriasis patients using a genome-wide association approach.

Methods: We recruited two independent cohorts of Chinese psoriasis patients administered etanercept biosimilar (with or without methotrexate). We identified 61 and 87 good responders (PASI improvement ≥75%), 19 and 10 poor responders (PASI improvement <50%) after 24 weeks treatment in the two cohorts, respectively. Then we performed genome-wide association studies (GWAS) on anti-TNF-α response in each cohort independently, followed by a fixed-effects inverse-variance meta-analysis in the 148 good and 29 poor responders.

Results: We tested genetic associations with >3 million genetic variants in either cohort. Meta-analysis identified significant associations within seven loci at p < 10⁻⁵, which also showed consistent association evidence in the two cohorts. These seven loci include rs2431355 (OR = 6.65, p = 4.46 × 10⁻⁷, IQGAP2-F2RL2 on 5q13.3), rs11801616 (OR = 0.11, p = 1.75 × 10⁻⁶, SDC3 on 1p35.2), rs3754679 (OR = 0.17, p = 7.71 × 10⁻⁶, CNOT11 on 2q11.2), rs13166823 (OR = 0.09, p = 3.71 × 10⁻⁶, IRF1-AS1 on 5q31.1), rs10220768 (OR = 5.49, p = 1.48 × 10⁻⁶, NPAP1 on 15q11.2), rs4796752 (OR = 5.56, p = 1.49 × 10⁻⁶, KRT31 on 17q21.2), and rs13045590 (OR = 0.08, p = 9.67 × 10⁻⁷, CTSZ on 20q13.3). Of the seven SNPs, six SNPs showed significant eQTL effect (p < 1 × 10⁻⁶) for several genes in multiple tissues.

Conclusion: These results suggest novel biological mechanisms and potential biomarkers for the response to anti-TNF therapies. These findings warrant further validation.