A Functional Ser326Cys Polymorphism in hOGG1 Is Associated with Noise-Induced Hearing Loss in a Chinese Population

Huanxi Shen,Lu Ding,Zhengdong Zhang,Kai Liu,Zhiqiang Hong,Qian Li,Cheng Du,Hengdong Zhang,Jinglian Cao,Baoli Zhu,Jian Shi,Giovanni Maga

doi:10.1371/journal.pone.0089662

Abstract

DNA damage to cochlear hair cells caused by 8-oxoguanine (8-oxoG) is essential for the development of noise-induced hearing loss (NIHL). Human 8-oxoG DNA glycosylase1 (hOGG1) is a key enzyme in the base excision repair (BER) pathway that eliminates 8-oxoG. Many epidemiological and functional studies have suggested that the hOGG1 Ser326Cys polymorphism (rs1052133) is associated with many diseases. The purpose of this investigation was to investigate whether the hOGG1 Ser326Cys polymorphism in the human BER pathway is associated with genetic susceptibility to NIHL in a Chinese population. This polymorphism was genotyped among 612 workers with NIHL and 615 workers with normal hearing. We found that individuals with the hOGG1 Cys/Cys genotype had a statistically significantly increased risk of NIHL compared with those who carried the hOGG1 Ser/Ser genotype (adjusted OR = 1.59, 95% CI = 1.13–2.25) and this increased risk was more pronounced among the workers in the 15- to 25- and >25-year noise exposure time, 85–92 dB(A) noise exposure level, ever smoking, and ever drinking groups, similar effects were also observed in a recessive model. In summary, our data suggested that the hOGG1 Cys/Cys genotype may be a genetic susceptibility marker for NIHL in the Chinese Han population.

Highlights

Noise-induced hearing loss (NIHL) is a common sensorineural impairment that is often caused by continuous and regular exposure to noise
Multivariate logistic regression analyses revealed that individuals with the Human 8-oxoG DNA glycosylase1 (hOGG1) Cys/Cys genotype had a 1.59-fold risk of NIHL compared with individuals carrying a Ser/Ser genotype
Gene-environment interactions were analyzed between the hOGG1 Cys/Cys genotype and NIHL risk factors, but no geneenvironment interactions were found in this study (P.0.05). In this case-control study, we found that the hOGG1 Cys/Cys genotype was statistically significantly associated with NIHL

Summary

Introduction

Noise-induced hearing loss (NIHL) is a common sensorineural impairment that is often caused by continuous and regular exposure to noise. NIHL is a leading occupational health risk in industrialised countries worldwide and the second most common form of sensorineural hearing impairment [1]. In the United States, 10 million people have noise-related hearing loss (http:// www.cdc.gov/NIOSH/), and in China, the number of workers with NIHL has increased 77.8% in the last three years (2010– 2012, http://www.aqsc.cn). NIHL is a complex disease that is induced by a combination of environmental and genetic factors. It is well known that noise, chemicals such as organic solvents, ototoxic substances (e.g., aminoglycosides), heat, vibrations, smoking, and medical factors (increased blood pressure, cholesterol, and reduced iris pigmentation) are risk factors for NIHL [2,3]. To identify susceptible workers and to develop new therapies that prevent NIHL, increasing new research is focused on an understanding of NIHL at the molecular level

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