NORA Manufacturing Sector Strategic Goals
927ZEXN - Genetic Modulation of Worker Susceptibility to Noise-Induced Hearing LossStart Date: 4/1/2008
End Date: 9/30/2009
Principal Investigator (PI)Name: Rickie Davis
Funded By: CDC National Office of Public Health Genomics
Primary Goal Addressed4.0
Secondary Goal Addressed
Attributed to Manufacturing
The purpose of this project is 1) to update the molecular biology capabilities of the DART laboratories and 2) determine if genetic factors can be determined which identify workers who have an increased susceptibility to noise-induced hearing loss. Partnering with the Department of the Navy, volunteers will provide biological samples which will be tested for genetic variation of seven pre-selected genes. These genes have been shown to code for proteins important for hearing. This project is based on seed money provided by the National Office of Public Health Genomics and will end on September 30, 2009.
The ultimate goal of this research is to reduce the incidence of NIHL by integrating genetic tests into worker safety programs. This would allow susceptible workers to receive additional resources (e.g. advanced training, high-tech hearing protection or additional monitoring) to reduce the occurrence of NIHL.
The present proposal has two specific aims. The first aim is to identify genetic variants of the candidate genes and develop assays to measure those variants in NIOSH laboratories. The second specific aim is to examine the candidate gene polymorphisms in susceptible and non-susceptible workers. Two genes will be examined because of their association with hearing (CDH23 [cadherin 23], GJB2 [connexin 26]), two genes because of their antioxidant roles (SOD2 [superoxide dismutase], PON2[paraoxynase]) and three genes because they have previously been identified as contributing to NIHL susceptibility (HSPA6 [heat shock protein], KCNQ4 [potassium recycling] and CAT[catalase].)
The present study will partner with the Department of the Navy to identify two civilian cohorts in their ship-building facilities. Based on utilizing existing audiograms collected as part of the Navy Hearing Conservation Program an experienced audiologist will:
1) Identify 150 of their most noise susceptible workers
2) Identify a matched cohort of 150 of resistant workers
Volunteers will provide a specimen for genotyping. Genomic DNA will be extracted. The 5' Nuclease (TaqMan® ) assay will be used for genotyping variants with an existing ABI Prism 7000 Sequence Detection System.
Allelic and expected genotype frequencies will be calculated. Goodness of fit of observed to expected genotype frequencies to Hardy-Weinberg proportions will be determined by X2 testing. Multiple logistic regression analyses will test for the association of genotype and risk of hearing loss greater than 15 dB at 4 kHz. Analyses will be conducted using SAS 9.1 software.
This effort will be successful if the resulting publications result in further research into the genetic bases of individual susceptibility to noise-induced hearing loss. These efforts should be measurable in citation reports.
In 2005 the NIOSH Hearing Loss Prevention Program under went peer review by the National Academies of Science Institute of Medicine. The peer review report was issued in 2006 recommended that Strategic Plan be developed for the Program. In 2007 the Program issued a Strategic Plan which included Intermediate Goal 5.2. "Prevent hearing loss by understanding individual susceptibility to noise." This project specifically addresses this Intermediate Strategic goal. By understanding factors which influence susceptibility to hearing loss, professionals can target interventions to reduce the burden of hearing loss by additional worker training, innovative technology and frequent audiometric follow up.
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