Paraoxonase 3 gene polymorphisms are associated with occupational noise-induced deafness: A matched case-control study from China

Abstract

Chronic exposure to noise is a detrimental environmental factor that can contribute to occupational noise-induced deafness (ONID) in industrial workers. ONID is caused by both environmental and genetic factors, and negatively impacts workers and manufacturing industries in China. Polymorphisms in the paraoxonase 2 gene (PON2) is associated with noise-induced hearing loss, and PON3 expression may modulate oxidative stress in cells and tissues by reducing the levels of reactive oxygen species, which are prominent in ONID. We conducted a matched case-control study to investigate whether PON3 polymorphisms and activity were associated with susceptibility to ONID. We genotyped PON3 single nucleotide polymorphisms (SNPs) using Sanger sequencing and measured the plasma PON3 activity using enzyme-linked immunosorbent assay. Conditional logistic regression models were fitted to evaluate the potential risk factors of ONID. A total of 300 subjects were included (n = 150 ONID and n = 150 control cases) from October 2017 to October 2019. We identified two types of genotypes for the PON3 SNPs. The independent risk factors for ONID were genotype CT and allele C with Odd's ratio (OR) = 2.12 (95% confidence interval [CI]: 1.18-3.84) and OR = 1.68 (95% CI: 1.06-2.66) for SNP rs11767787; AG and allele A with OR = 2.09 (95% CI: 1.25-3.47) and OR = 1.87 (95% CI: 1.19-2.93) for SNP rs13226149; and CT and allele T with OR = 2.59 (95% CI: 1.44-4.67) and OR = 1.95 (95% CI: 1.22-3.14) for SNP rs17882539, respectively. Furthermore, the plasma PON3 level (> 1504 U/L) was observed to be a protective factor associated with the lowest level of ONID (less than 991 U/L) after adjusting for confounding factors (OR = 0.27, 95% CI: 0.13-0.54). In conclusion, the PON3 polymorphisms rs11767787, rs13226149, and rs17882539 and plasma PON3 activity are associated with susceptibility to ONID in the Chinese population.

Fig 1. Mean differences in hearing thresholds between ONID and control groups at all frequencies.

The differences of hearing thresholds between ONID and control group at frequency 3.0, 4.0 and 6.0 kHz were observed to be stable. Data are expressed as mean difference.

Fig 2. The electrophoresis of PON3 PCR amplicons for gene.

(A) rs11767787, (B) rs13226149 (C) rs17882539.

Fig 3. Distributions of plasma PNO3 activity in the ONID and control groups for rs11767787, rs13226149 and rs17882539, and combined, respectively.

Red bars represent control group and blue bars represent ONID cases. The genotypes are indicated below each bar chart. A showed PON3 activity at rs11767787, B showed PON3 activity at rs13226149, C showed PON3 activity at rs17882539, and D showed PON3 activity at three SNPs combined.

Fig 4. The risk of plasma PON3 activity is associated with ONID in four groups.

The exposure plasma PNO3 activity was categorized into four groups (less than P₂₅, P₂₅-P₅₀, P₅₀-P₇₅, greater than P₇₅), considering the lowest group as the reference.