Li Xiuting, Cao Jinglian, Wang Jun, Song Haiyan, Ji Guixiang, Dong Qiu, Wei Chunlong, Cao Ying, Wang Boshen, Zhu Baoli, Xiao Hang
1 Key Lab of Modern Toxicology, Ministry of Education, Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China ; 2 Department of Science and Education, Nanjing Prevention and Treatment Center for Occupational Diseases, Nanjing, China ; 3 Center of Prevention and Health Care, the Forth People's Hospital of Kunshan City, Suzhou, China ; 4 Ministry of Environmental Protection, Nanjing Institute of Environmental Sciences/Key Laboratory of Pesticide Environmental Assessment and Pollution Control, Nanjing, China ; 5 Department of ENT, Huai'an Second People's Hospital, Huai'an, China ; 6 Institute of Occupational Disease Prevention, Jiangsu Provincial Center for Disease Prevention and Control, Nanjing, China.
J Thorac Dis. 2016 Mar;8(3):430-8. doi: 10.21037/jtd.2016.02.26.
Noise-induced hearing loss (NIHL) is a complex disease induced by a combination of genetic and environmental factors. Paraoxonase2 (PON2) gene involved in the regulation of reactive oxygen species, and affecting the vulnerability of cochlea to NIHL, and ATPase, calcium-transporting, plasma membrane 2 (ATP2B2) gene which encodes plasma membrane calcium-transporting ATPase isoform 2 (PMCA2) are the candidate genes relating to the attack of NIHL. In this study, we investigated whether ATP2B2 and PON2 polymorphisms were associated with NIHL in Chinese of Han nationality population.
We performed a case-control study between six single nucleotide polymorphisms (SNPs) (rs1719571, rs3209637 and rs4327369 within ATP2B2, rs12026, rs7785846 and rs12704796 within PON2) and NIHL in 454 subjects. All the SNPs were genotypes, using the TaqMan MGB probe assay. Odds ratios (ORs) were calculated with 95% confidence intervals (95% CIs) with logistic regression analysis to test the level of association for SNPs.
In our study, 221 subjects with hearing loss and 233 subjects without hearing loss were recruited. The frequencies of the CG and CG + GG genotype of rs12026 (PON2) conferred risk factors for NIHL with adjusted OR values of 2.62 (95% CI, 1.69-4.06) and 2.48 (95% CI, 1.63-3.78), respectively. This kind of significance was also found at locus rs7785846, where genotypes CT and CT + TT were the risk types, with adjusted ORs of 2.52 (95% CI, 1.62-3.93) and 2.35 (95% CI, 1.54-3.58), respectively. We performed stratified analysis per noise exposure level, when it came to rs7785846 and rs12026 in the >92 dB(A) noise exposure group, the subjects who carried heterozygote were of significantly (P<0.01) higher susceptibility to NIHL than homozygote carriers. By contrast, no significantly higher risk was found for any rs12704796 genotypes or any genotypes in ATP2B2 (P>0.05), which may suggest that these SNPs did not have significant effects on noise susceptibility across noise exposure.
Our research suggested that PON2 might play a role in the etiology of NIHL in Chinese of Han nationality population.
噪声性听力损失（NIHL）是一种由遗传和环境因素共同作用引起的复杂疾病。对氧磷酶2（PON2）基因参与活性氧的调节，并影响耳蜗对NIHL的易感性，而编码质膜钙转运ATP酶同工型2（PMCA2）的质膜钙转运ATP酶2（ATP2B2）基因是与NIHL发病相关的候选基因。在本研究中，我们调查了ATP2B2和PON2基因多态性是否与汉族人群中的NIHL相关。
我们对454名受试者中六个单核苷酸多态性（SNP）（ATP2B2内的rs1719571、rs3209637和rs4327369，PON2内的rs12026、rs7785846和rs12704796）与NIHL进行了病例对照研究。所有SNP均采用TaqMan MGB探针法进行基因分型。通过逻辑回归分析计算比值比（OR）及95%置信区间（95%CI），以检验SNP的关联水平。
在我们的研究中，招募了221名听力损失受试者和233名无听力损失受试者。rs12026（PON2）的CG和CG + GG基因型频率是NIHL的危险因素，校正后的OR值分别为2.62（95%CI，1.69 - 4.06）和2.48（95%CI，1.63 - 3.78）。在rs7785846位点也发现了这种显著性，其中CT和CT + TT基因型是风险类型，校正后的OR分别为2.52（95%CI，1.62 - 3.93）和2.35（95%CI，1.54 - 3.58）。我们按噪声暴露水平进行了分层分析，在>92 dB(A)噪声暴露组中，当涉及rs7785846和rs12026时，携带杂合子的受试者对NIHL的易感性显著高于纯合子携带者（P<0.01）。相比之下，未发现rs12704796的任何基因型或ATP2B2的任何基因型有显著更高的风险（P>0.05），这可能表明这些SNP对不同噪声暴露水平下的噪声易感性没有显著影响。
我们的研究表明，PON2可能在汉族人群NIHL的病因学中起作用。
