Date of Award

9-13-2010

Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)

First Advisor

Mark Russi

Second Advisor

Lloyd Cantley

Abstract

Occupational exposure-related hearing loss is a significant health concern for affected workers. Organic solvent exposure has emerged as an important contributor to hearing loss. It is thought that hearing loss related to solvent and noise exposure is mediated by reactive oxygen species (ROS). The glutathione associated enzymes and the manganese superoxide dismutase enzymes (SOD2) are important components of the cochlear hair cellâs defense against oxidative stress. This study is aimed to determine whether polymorphisms within the glutathione S-transferases (GST) P1 and GSTM1, glutathione peroxidase 1 (GPX1), and SOD2 are associated with hearing status in solvent exposed factory workers. Genotypes for the GSTM1 + vs. null, GSTP1 Ile105Val, GPX1 Pro198Leu, SOD2 Val16Ala polymorphisms along with hearing status were determined in factory workers exposed to organic solvents. Hearing tests consisted of pure tone audiometric (PTA) thresholds from 3-6 kHz and distortion product otoacoustic emissions (DPOAEs) for 3-6 kHz. Bivariate and multivariate regression analysis was undertaken to assess for association between polymorphisms and hearing outcomes. The GSTP1 Val/Ile genotype at position 105 was associated with higher PTA thresholds (β=12.41, P value= 0.01) from 3-6 kHz in workers below age 22-43. The analysis showed a protective association of the SOD2 Ala/Val genotype (β= -26.42, P value= 0.025) and The GPX1 Leu/Leu genotypes (β=47.81, P value= 0.034) with audiometric thresholds from 3-6 kHz in individuals above age 43. This small cross-sectional study suggests that polymorphisms within the antioxidant system may alter susceptibility to hearing loss in workers exposed to organic solvents. These results also suggest the mechanisms by which this affect are mediated are complex and should be further investigated.

Share

COinS