Genetic polymorphisms of TRPA1 does affect risk of cisplatin induced nephrotoxicity in Chinese population

TRPA1基因多态性确实会影响中国人群顺铂诱导肾毒性的风险

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Abstract

INTRODUCTION: Irreversible acute kidney injury (AKI) caused by cisplatin limits its clinical use, and transient receptor potential anchor protein 1 (TRPA1) regulates cisplatin-induced nephrotoxicity (CIN) through NF-κB signaling pathway-mediated inflammation. Single nucleotide polymorphisms in TRPA1 and NF-κB1 genes may be associated with individual heterogeneous nephrotoxicity. MATERIALS AND METHODS: In this paper, we investigated the association of 17 single nucleotide polymorphisms (SNP) of TRPA1 and NF-κB1 genes with cisplatin-induced acute nephrotoxicity. Nephrotoxicity and its severity were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE 5.0). SNPs were measured by 48-Plex SNPscan® high-throughput SNP typing echnology in DNA isolated from peripheral blood of 589 Chinese Han lung cancer patients (241 with CIN and 348 without CIN) treated with cisplatin regimen. RESULTS: TRAP1 gene rs920829 locus T allele carriers had a reduced risk of nephrotoxicity relative to C allele carriers (OR 0.684, 95 % CI 0.524-0.894, p = 0.003), and their additive and dominant models showed similar trends as well. However, the SNPs of NF-κB1 were not observed to be correlated with nephrotoxicity. CONCLUSION: SNPs of TRPA1 have the potential as biomarkers for predicting cisplatin nephrotoxicity.

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