CARD8 polymorphism rs2043211 protects against noise-induced hearing loss by causing the dysfunction of CARD8 protein
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RESEARCH ARTICLE
CARD8 polymorphism rs2043211 protects against noise-induced hearing loss by causing the dysfunction of CARD8 protein Long Miao 1 & Boshen Wang 1 & Jiahui Ji 1 & Liu Wan 1 & Lihong Yin 1 & Baoli Zhu 2 & Juan Zhang 1 & Yuepu Pu 1 Received: 17 June 2020 / Accepted: 7 October 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Inflammation is a complicated process and is considered to be responsible for the development of noise-induced hearing loss (NIHL). CARD8 is an important component of inflammasome that has been implicated in inflammation. To decide the relationship between the polymorphisms of CARD8 gene and NIHL risk and deduce the potential mechanism, three SNPs (rs2043211, rs1062808, and rs12459322) were genotyped in a Chinese population consisting of 610 NIHL cases and 612 normal hearing controls. The possible impacts of SNPs on CARD8 structure and function were assessed using a variety of bioinformatics tools. Plasmids expressing wild-type and/or mutated CARD8 were transfected into HEK293 cells to verify the effect of SNPs on CARD8 protein expression level by western blot. The results revealed that rs2043211 AA genotype and A allele were associated with decreased risk of NIHL. Stratified analysis found that the male, drinking and exposed to noise ≥ 92 dB, subjects harboring rs2043211 A allele had a low risk of NIHL. The haplotype AGG (rs2043211-rs1062808-rs12459322) was significantly associated with a decreased risk of NIHL. SNP rs2043211 was predicted to be deleterious and affects CARD8 protein structure and stability. Furthermore, the functional experiment showed the mutant CARD8 could significantly decrease the CARD8 protein expression level. This study confirms that rs2043211 A allele may reduce NIHL risk by causing the loss of PPI combined with the decreased CARD8 expression level leading to CARD8 functional changes, and it may be one valuable genetic biomarker of NIHL susceptibility for Chinese noise-exposed workers. Keywords Noise-induced hearing loss . CARD8 . Polymorphism . In silico analysis . Susceptibility . Biomarker
Introduction Globally, noise-induced hearing loss (NIHL) is the most common occupation-related disease and the second leading form Responsible Editor: Lotfi Aleya Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11356-020-11193-1) contains supplementary material, which is available to authorized users. * Juan Zhang [email protected] * Yuepu Pu [email protected] 1
Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, People’s Republic of China
2
Department of Prevention and Control for Occupational Disease, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing 210009, People’s Republic of China
of sensorineural hearing defect in humans (Miao et al. 2019). The World Health Organization (WHO) previously reported that approximately 10% of individuals worldwide that are exposed to noise may deve
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