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CARD8 polymorphism rs2043211 protects against noise-induced hearing loss by causing the dysfunction of CARD8 protein

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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.

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Data availability

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

References

  • Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, Kondrashov AS, Sunyaev SR (2010) A method and server for predicting damaging missense mutations. Nat Methods 7:248–249

    Article  CAS  Google Scholar 

  • Arshad M, Bhatti A, John P (2018) Identification and in silico analysis of functional SNPs of human TAGAP protein: a comprehensive study. PLoS One 13:e0188143

    Article  Google Scholar 

  • Barrett JC, Fry B, Maller J, Daly MJ (2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21:263–265

    Article  CAS  Google Scholar 

  • Basner M, Babisch W, Davis A, Brink M, Clark C, Janssen S, Stansfeld S (2014) Auditory and non-auditory effects of noise on health. Lancet 383:1325–1332

    Article  Google Scholar 

  • Capriotti E, Altman RB (2011) Improving the prediction of disease-related variants using protein three-dimensional structure. BMC Bioinformatics 12(Suppl 4):S3

    Article  CAS  Google Scholar 

  • Capriotti E, Fariselli P, Casadio R (2005) I-Mutant2.0: predicting stability changes upon mutation from the protein sequence or structure. Nucleic Acids Res 33:W306–W310

    Article  CAS  Google Scholar 

  • Carugo O, Pongor S (2001) A normalized root-mean-square distance for comparing protein three-dimensional structures. Protein Sci 10:1470–1473

    Article  CAS  Google Scholar 

  • Chen Y, Ren X, Li C, Xing S, Fu Z, Yuan Y, Wang R, Wang Y, Lv W (2015) CARD8 rs2043211 polymorphism is associated with gout in a Chinese male population. Cell Physiol Biochem 35:1394–1400

    Article  CAS  Google Scholar 

  • Cooper GM, Goode DL, Ng SB, Sidow A, Bamshad MJ, Shendure J, Nickerson DA (2010) Single-nucleotide evolutionary constraint scores highlight disease-causing mutations. Nat Methods 7:250–251

    Article  CAS  Google Scholar 

  • da Silva WC, Oshiro TM, de Sa DC, Franco DD, Festa Neto C, Pontillo A (2016) Genotyping and differential expression analysis of inflammasome genes in sporadic malignant melanoma reveal novel contribution of CARD8, IL1B and IL18 in melanoma susceptibility and progression. Cancer Genet 209:474–480

    Article  Google Scholar 

  • Dalton DS, Cruickshanks KJ, Klein BE, Klein R, Wiley TL, Nondahl DM (2003) The impact of hearing loss on quality of life in older adults. Gerontologist 43:661–668

    Article  Google Scholar 

  • Fisher SA, Mirza MM, Onnie CM, Soars D, Lewis CM, Prescott NJ, Mathew CG, Sanderson J, Forbes A, Todhunter C, Donaldson P, Mansfield J (2007) Combined evidence from three large British association studies rejects TUCAN/CARD8 as an IBD susceptibility gene. Gastroenterology 132:2078–2080

    Article  Google Scholar 

  • Garcia-Bermudez M, Lopez-Mejias R, Gonzalez-Juanatey C, Corrales A, Castaneda S, Ortiz AM, Miranda-Filloy JA, Gomez-Vaquero C, Fernandez-Gutierrez B, Balsa A, Pascual-Salcedo D, Blanco R, Llorca J, Martin J, Gonzalez-Gay MA (2013) CARD8 rs2043211 (p.C10X) polymorphism is not associated with disease susceptibility or cardiovascular events in Spanish rheumatoid arthritis patients. DNA Cell Biol 32:28–33

    Article  CAS  Google Scholar 

  • Guo H, Ding E, Sheng R, Cheng J, Cai W, Guo J, Wang N, Zhang H, Zhu B (2018) Genetic variation in KCNQ4 gene is associated with susceptibility to noise-induced hearing loss in a Chinese population. Environ Toxicol Pharmacol 63:55–59

    Article  CAS  Google Scholar 

  • Honkura Y, Matsuo H, Murakami S, Sakiyama M, Mizutari K, Shiotani A, Yamamoto M, Morita I, Shinomiya N, Kawase T, Katori Y, Motohashi H (2016) NRF2 is a key target for prevention of noise-induced hearing loss by reducing oxidative damage of cochlea. Sci Rep 6:19329

    Article  CAS  Google Scholar 

  • Jamesdaniel S, Hu B, Kermany MH, Jiang H, Ding D, Coling D, Salvi R (2011) Noise induced changes in the expression of p38/MAPK signaling proteins in the sensory epithelium of the inner ear. J Proteome 75:410–424

    Article  CAS  Google Scholar 

  • Kastbom A, Johansson M, Verma D, Soderkvist P, Rantapaa-Dahlqvist S (2010) CARD8 p.C10X polymorphism is associated with inflammatory activity in early rheumatoid arthritis. Ann Rheum Dis 69:723–726

    Article  CAS  Google Scholar 

  • Kelley LA, Mezulis S, Yates CM, Wass MN, Sternberg MJ (2015) The Phyre2 web portal for protein modeling, prediction and analysis. Nat Protoc 10:845–858

    Article  CAS  Google Scholar 

  • Kumar P, Henikoff S, Ng PC (2009) Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm. Nat Protoc 4:1073–1081

    Article  CAS  Google Scholar 

  • Kumar A, Rajendran V, Sethumadhavan R, Shukla P, Tiwari S, Purohit R (2014) Computational SNP analysis: current approaches and future prospects. Cell Biochem Biophys 68:233–239

    Article  CAS  Google Scholar 

  • Liu YM, Li XD, Guo X, Liu B, Lin AH, Ding YL, Rao SQ (2010) SOD2 V16A SNP in the mitochondrial targeting sequence is associated with noise induced hearing loss in Chinese workers. Dis Markers 28:137–147

    Article  Google Scholar 

  • McGovern DP, Butler H, Ahmad T, Paolucci M, van Heel DA, Negoro K, Hysi P, Ragoussis J, Travis SP, Cardon LR, Jewell DP (2006) TUCAN (CARD8) genetic variants and inflammatory bowel disease. Gastroenterology 131:1190–1196

    Article  CAS  Google Scholar 

  • Miao L, Ji J, Wan L, Zhang J, Yin L, Pu Y (2019) An overview of research trends and genetic polymorphisms for noise-induced hearing loss from 2009 to 2018. Environ Sci Pollut Res Int 26:34754–34774

    Article  Google Scholar 

  • Miller JM, Brown JN, Schacht J (2003) 8-iso-prostaglandin F(2alpha), a product of noise exposure, reduces inner ear blood flow. Audiol Neurootol 8:207–221

    Article  CAS  Google Scholar 

  • Murai N, Kirkegaard M, Jarlebark L, Risling M, Suneson A, Ulfendahl M (2008) Activation of JNK in the inner ear following impulse noise exposure. J Neurotrauma 25:72–77

    Article  Google Scholar 

  • Paramel GV, Sirsjo A, Fransen K (2015) Role of genetic alterations in the NLRP3 and CARD8 genes in health and disease. Mediat Inflamm 2015:846782

    Article  CAS  Google Scholar 

  • Patel M, Hu Z, Bard J, Jamison J, Cai Q, Hu BH (2013) Transcriptome characterization by RNA-Seq reveals the involvement of the complement components in noise-traumatized rat cochleae. Neuroscience 248:1–16

    Article  CAS  Google Scholar 

  • Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, Ferrin TE (2004) UCSF chimera--a visualization system for exploratory research and analysis. J Comput Chem 25:1605–1612

    Article  CAS  Google Scholar 

  • Radivojac P, Vacic V, Haynes C, Cocklin RR, Mohan A, Heyen JW, Goebl MG, Iakoucheva LM (2010) Identification, analysis, and prediction of protein ubiquitination sites. Proteins 78:365–380

    Article  CAS  Google Scholar 

  • Razmara M, Srinivasula SM, Wang L, Poyet JL, Geddes BJ, DiStefano PS, Bertin J, Alnemri ES (2002) CARD-8 protein, a new CARD family member that regulates caspase-1 activation and apoptosis. J Biol Chem 277:13952–13958

    Article  CAS  Google Scholar 

  • Shi YY, He L (2005) SHEsis, a powerful software platform for analyses of linkage disequilibrium, haplotype construction, and genetic association at polymorphism loci. Cell Res 15:97–98

    Article  CAS  Google Scholar 

  • Singh SM, Kongari N, Cabello-Villegas J, Mallela KM (2010) Missense mutations in dystrophin that trigger muscular dystrophy decrease protein stability and lead to cross-beta aggregates. Proc Natl Acad Sci U S A 107:15069–15074

    Article  CAS  Google Scholar 

  • von Mering C, Huynen M, Jaeggi D, Schmidt S, Bork P, Snel B (2003) STRING: a database of predicted functional associations between proteins. Nucleic Acids Res 31:258–261

    Article  Google Scholar 

  • Wang B, Ding E, Shen H, Wang J, Sun K, Chen S, Han L, Zhang H, Zhu B, Xu M (2017) Association of TagSNP in lncRNA HOTAIR with susceptibility to noise-induced hearing loss in a Chinese population. Hear Res 347:41–46

    Article  CAS  Google Scholar 

  • Wesselius A, Bours MJ, Arts IC, Theunisz EH, Geusens P, Dagnelie PC (2012) The P2X(7) loss-of-function Glu496Ala polymorphism affects ex vivo cytokine release and protects against the cytotoxic effects of high ATP-levels. BMC Immunol 13:64

    Article  CAS  Google Scholar 

  • Xie HW, Qiu W, Heyer NJ, Zhang MB, Zhang P, Zhao YM, Hamernik RP (2016) The use of the kurtosis-adjusted cumulative noise exposure metric in evaluating the hearing loss risk for complex noise. Ear Hear 37:312–323

    Article  Google Scholar 

  • Yang S, Cai Q, Vethanayagam RR, Wang J, Yang W, Hu BH (2016) Immune defense is the primary function associated with the differentially expressed genes in the cochlea following acoustic trauma. Hear Res 333:283–294

    Article  CAS  Google Scholar 

  • Zhang Y, Skolnick J (2005) TM-align: a protein structure alignment algorithm based on the TM-score. Nucleic Acids Res 33:2302–2309

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank every worker for their participations in this study.

Funding

This study was supported by the Jiangsu Preventive Medicine Foundation (Y2015049).

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Authors and Affiliations

  1. Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, People’s Republic of China

    Long Miao, Boshen Wang, Jiahui Ji, Liu Wan, Lihong Yin, Juan Zhang & Yuepu Pu

  2. Department of Prevention and Control for Occupational Disease, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, 210009, People’s Republic of China

    Baoli Zhu

Authors
  1. Long Miao
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  2. Boshen Wang
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  3. Jiahui Ji
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  4. Liu Wan
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  5. Lihong Yin
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  6. Baoli Zhu
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  7. Juan Zhang
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  8. Yuepu Pu
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Contributions

JZ and YP contributed to the study conception and design. LM, BW, JJ, and LW performed material preparation and data collection. LM and BW contributed to data analysis and interpretation. LM drafted the manuscript. LY, BZ, JZ, and YP critically reviewed and revised the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Juan Zhang or Yuepu Pu.

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The authors declare that they have no conflicts of interest.

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This study was approved by the institutional review board of Jiangsu Provincial Center for Disease Prevention and Control.

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Informed consent was obtained from all individual participants included in the study.

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The participant has consented to the submission of the case report to the journal.

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Responsible Editor: Lotfi Aleya

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Miao, L., Wang, B., Ji, J. et al. CARD8 polymorphism rs2043211 protects against noise-induced hearing loss by causing the dysfunction of CARD8 protein. Environ Sci Pollut Res 28, 8626–8636 (2021). https://doi.org/10.1007/s11356-020-11193-1

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  • DOI: https://doi.org/10.1007/s11356-020-11193-1

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