Association of genetic variations in FOXO3 gene with susceptibility to noise induced hearing loss in a Chinese population

PLOS ONE, Nov 2019

Noise induced hearing loss (NIHL), a multifactorial disease involving both genetic and environmental factors, is one of the most important occupational health hazards. Nonetheless, the influence of FOXO3 variants on NIHL risk have not been illuminated. This research was conducted to explore the effects of FOXO3 polymorphisms on individual susceptibility to NIHL. A total of 2689 industrial workers from one textile factory of east China were recruited to participate in the current research. Venous blood was collected, questionnaire and pure-tone audiometry (PTA) was conducted by specialist physicians. Then, we performed genotyping of three selected SNPs (rs2802292, rs10457180, and rs12206094) in FOXO3 gene in 566 NIHL patients and 566 controls. Subsequently, the main effects of genotype and its interactions were evaluated. Our results revealed that individuals with the G allele of rs2802292, G allele of rs10457180, T allele of rs12206094 (OR = 1.43, 1.43, and 1.31 respectively) and the haplotype GAC and others (TGT/GGT/GGC/GAT) (rs2802292-rs10457180-rs12206094) (OR = 1.49 and 2.09 respectively) are associated with an increased risk of NIHL in a Chinese population. Stratified analysis showed that an increased NIHL risk was found in the subjects who exposed to noise >16 years with rs2802292 GG/GT and rs10457180 AG/GG genotype with an OR of 1.62 and 1.66 respectively. Multifactor dimensionality reduction analysis indicated that rs10457180, rs2802292, and rs12206094 have interactions and are related to increased NIHL risk (OR = 1.53). The genetic polymorphism rs2802292, rs10457180, and rs12206094 within FOXO3 gene are associated with an increased risk of NIHL in a Chinese population and have potential to be biomarkers for noise exposed workers.

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Association of genetic variations in FOXO3 gene with susceptibility to noise induced hearing loss in a Chinese population

December Association of genetic variations in FOXO3 gene with susceptibility to noise induced hearing loss in a Chinese population Haoran Guo 0 1 Enmin Ding 1 Ying Bai 1 Hengdong Zhang 1 Huanxi Shen 1 Jun Wang 0 1 Xianping Song 1 Wenyan Cai 1 Jiadi Guo 1 Baoli Zhu 0 1 ☯ These authors contributed equally to this work. 1 1 0 School of Public Health, Southeast University , Nanjing, Jiangsu Province , China , 2 Institute of Occupational Disease Prevention, Jiangsu Provincial Center for Disease Prevention and Control , Nanjing, Jiangsu Province , China , 3 Kunshan Centers for Disease Prevention and Control , Kunshan, Jiangsu Province , China , 4 School of Public Health, Nanjing Medical University , Nanjing, Jiangsu Province , China 1 Editor: Qingyi Wei, Duke Cancer Institute , UNITED STATES Noise induced hearing loss (NIHL), a multifactorial disease involving both genetic and environmental factors, is one of the most important occupational health hazards. Nonetheless, the influence of FOXO3 variants on NIHL risk have not been illuminated. This research was conducted to explore the effects of FOXO3 polymorphisms on individual susceptibility to NIHL. A total of 2689 industrial workers from one textile factory of east China were recruited to participate in the current research. Venous blood was collected, questionnaire and pure-tone audiometry (PTA) was conducted by specialist physicians. Then, we performed genotyping of three selected SNPs (rs2802292, rs10457180, and rs12206094) in FOXO3 gene in 566 NIHL patients and 566 controls. Subsequently, the main effects of genotype and its interactions were evaluated. Our results revealed that individuals with the G allele of rs2802292, G allele of rs10457180, T allele of rs12206094 (OR = 1.43, 1.43, and 1.31 respectively) and the haplotype GAC and others (TGT/GGT/GGC/GAT) (rs2802292-rs10457180-rs12206094) (OR = 1.49 and 2.09 respectively) are associated with an increased risk of NIHL in a Chinese population. Stratified analysis showed that an increased NIHL risk was found in the subjects who exposed to noise >16 years with rs2802292 GG/GT and rs10457180 AG/GG genotype with an OR of 1.62 and 1.66 respectively. Multifactor dimensionality reduction analysis indicated that rs10457180, rs2802292, and rs12206094 have interactions and are related to increased NIHL risk (OR = 1.53). The genetic polymorphism rs2802292, rs10457180, and rs12206094 within FOXO3 gene are associated with an increased risk of NIHL in a Chinese population and have potential to be biomarkers for noise exposed workers. - Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Funding: Baoli Zhu was funded by Jiangsu Province's Outstanding Medical Academic Leader program (CXTDA2017029) and Huanxi Shen was funded by Jiangsu Program for Young Medical Talents (QNRC2016528). Competing interests: The authors have declared that no competing interests exist. Introduction Occupational noise is one of the most common occupational hazards for the health of industrial workers, and noise induced hearing loss (NIHL) is the second most frequent form of sensorineural hearing impairment besides age-related hearing loss (ARHL) worldwide[1]. It has been verified that NIHL is a kind of multifactorial disease resulting from the interactions of both genetic and environmental factors[ 2 ]. Currently, the mechanism of NIHL has not been completely understood. The possible etiopathogenesis may involve the inner ear cell apoptosis or necrosis caused by oxidative stress or the metabolic products generated during signal transduction and direct mechanical injury to the structures of the cochlea[3±5]. However, numerous population studies have indicated that the subjects had various degrees of NIHL risk even if they were exposed to equal noise intensity level[ 1, 6 ]. Animal experiments also prove that genetic variations contribute to the incidence of NIHL[ 7, 8 ]. Previous studies have found that single nucleotide polymorphism (SNPs) in HSP70, EYA4, CDH23, GRHL2 and DFNA5 genes are associated with human genetic susceptibility to NIHL and could increase or decrease the risk of NIHL by interaction with occupational noise[9±11]. All the evidence implicates that the genetic susceptibility and its interaction with environmental factors might play an important role in the occurrence and development of NIHL. Forkhead Box O3 (FOXO3) is a winged helix transcription factor that has been known to regulate longevity in various species including humans and mice[12±14]. FOXO3 regulates the expression of stress response proteins[ 15 ] and FOXO3 effectors may ameliorate oxidative stress, block mitosis, induce apoptosis, or promote inflammation[ 16 ]. It has been shown that mice are susceptible to adult-onset hearing loss with the hallmark characteristics of auditory neuropathy, namely, elevated auditory thresholds combined with normal outer hair cell function if lacking the transcri (...truncated)


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Haoran Guo, Enmin Ding, Ying Bai, Hengdong Zhang, Huanxi Shen, Jun Wang, Xianping Song, Wenyan Cai, Jiadi Guo, Baoli Zhu. Association of genetic variations in FOXO3 gene with susceptibility to noise induced hearing loss in a Chinese population, PLOS ONE, 2017, Volume 12, Issue 12, DOI: 10.1371/journal.pone.0189186