The Association Study Between CAT Polymorphisms And Noise-induced Hearing Loss In A Chinese Population

Noise-induced hearing loss (NIHL) is one of the world-wide high occupationalhazards which caused by repeated or continuous expose to high levels of noise, and itis the second most frequent form of sensorineural hearing loss, after age-relatedhearing loss (ARHL). NIHL can affect the quality of life in workers and bring outpsychosocial problems such as isolation, depression and an increased likelihood ofaccidents. The large individual variability in susceptibility to noise is one of the mostremarkable features of NIHL which induced by a combination of genetic andenvironmental factors. Cochlear hair cell damage and death by reactive oxygenspecies (ROS) as a result of exposure to noise is a potential mechanism for NIHL.Catalase, an important cellular antioxidant, composed the primary antioxidant defenseagainst ROS and converted to nonreactive molecules by endogenous cellular enzymes.Since inter-individual variation in antioxidant capacity may occur as a result offunctional SNPs of gene regulating antioxidant enzyme activity, it was hypothesizedthat such polymorphisms of CAT might be related to the development of NIHL.Therefore, we indicated that CAT may be a susceptible gene for NIHL.The study group was recruited from noise-exposed workers of a coal mine, a chemical fibre factory and a machinery works which from the cities of Xuzhou,Yizheng, Nanjing in Jiangsu province, China, during the period from October2010toMay2011. Finally,615cases and1514controls were recruited,644matchingcontrols. Venous blood samples (5ml) were collected and plasma were separated.Genomic DNA was isolated from mononuclear cells from peripheral blood withTianGen DNA extraction Kit (Beijing, China). SNPs were selected in the functionalregion of the CAT from the NCBI database (http://www.ncbi.nlm.nih.gov/pubmed/).Finally, rs564250, rs769214, rs7943316and rs769217were selected. The ABI7900HT real time PCR system was performed for SNP genotyping, and the activity ofCAT was determined by using commercially available kits. We used multivariateregression analysis, with adjustments for the possible confounding variables to obtainadjusted odds ratios (ORs) for risk of NIHL and their95%confidence intervals (CIs).The significantly differences of CAT activity were found in cases and controls (P=0.045). In total population, the distribution of the all SNPs were not significantlydifferent between the cases and controls; Dominant genetic model were build forstratification, compared with rs564250CC genotypes, the combined genotypesrs564250CT/TT had a significantly decreased of NIHL risk in young (OR=0.47,95%CI=0.27-0.80), no smoking (OR=0.64,95%CI=0.44-0.93), women (OR=0.27,95%CI=0.11-0.66) population; For rs769214and rs7943316, the protect effectwere found for smoking population who carrying the combined genotypes (OR=0.69,95%CI=0.52-0.93for rs769214; OR=0.73,95%CI=0.55-0.98for rs7943316). Insmoking population, for rs769214polymorphism, multivariate logistic regressionanalysis indicated that the heterozygous AG and variant AA genotypes wereassociated with a significant lower risk of NIHL, compared with the wild-type GGgenotypes (adjusted OR=0.73,95%CI=0.54-0.99for AG and adjusted OR=0.50,95%CI=0.29-0.87for AA). Further stratification analysis showed that this decreaserisk was more prominent among subgroup of workers with expose time≤20years inthe two SNPs (adjusted OR=0.65,95%CI=0.45-0.96for rs769214; adjusted OR=0.67,95%CI=0.46-0.98for rs7943316). For the subgroup of exposure level>92dB,a significant decreased risk also can be observed in rs7943316(adjusted OR=0.51, 95%CI=0.32-0.83).These findings suggested that the CAT polymorphism may be a geneticsusceptibility marker for NIHL among Chinese smokers. Further functionalevaluations and larger molecular epidemiological studies will contribute to confirmthe potential mechanism of NIHL.