Dataset Information

Cumulative lead exposure and age-related hearing loss: the VA Normative Aging Study.

ABSTRACT: Although lead has been associated with hearing loss in occupational settings and in children, little epidemiologic research has been conducted on the impact of cumulative lead exposure on age-related hearing loss in the general population. We determined whether bone lead levels, a marker of cumulative lead exposure, are associated with decreased hearing ability in 448 men from the Normative Aging Study, seen between 1962 and 1996 (2264 total observations). Air conduction hearing thresholds were measured at 0.25-8 kHz and pure-tone averages (PTA) (mean of 0.5, 1, 2 and 4 kHz) were computed. Tibia and patella lead levels were measured using K X-ray fluorescence between 1991 and 1996. In cross-sectional analyses, after adjusting for potential confounders including occupational noise, patella lead levels were significantly associated with poorer hearing thresholds at 2, 3, 4, 6 and 8 kHz and PTA. The odds of hearing loss significantly increased with patella lead levels. We also found significant positive associations between tibia lead and the rate change in hearing thresholds at 1, 2, and 8 kHz and PTA in longitudinal analyses. Our results suggest that chronic low-level lead exposure may be an important risk factor for age-related hearing loss and reduction of lead exposure could help prevent or delay development of age-related hearing loss.

SUBMITTER: Park SK

PROVIDER: S-EPMC2934752 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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Cumulative lead exposure and age-related hearing loss: the VA Normative Aging Study.

Park Sung Kyun SK Elmarsafawy Sahar S Mukherjee Bhramar B Spiro Avron A Vokonas Pantel S PS Nie Huiling H Weisskopf Marc G MG Schwartz Joel J Hu Howard H

Hearing research 20100716 1-2

Although lead has been associated with hearing loss in occupational settings and in children, little epidemiologic research has been conducted on the impact of cumulative lead exposure on age-related hearing loss in the general population. We determined whether bone lead levels, a marker of cumulative lead exposure, are associated with decreased hearing ability in 448 men from the Normative Aging Study, seen between 1962 and 1996 (2264 total observations). Air conduction hearing thresholds were ...[more]

PMID: 20638461

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Project description:BackgroundPrevious evidence has indicated CMP-Neu5Ac hydroxylase (Cmah) disruption inducesaging-related hearing loss (AHL). However, its function mechanisms remain unclear. This study was to explore the mechanisms of AHL by using microarray analysis in the Cmah deficiency animal model.MethodsMicroarray dataset GSE70659 was available from the Gene Expression Omnibus database, including cochlear tissues from wild-type and Cmah-null C57BL/6J mice with old age (12 months, n = 3). Differentially expressed genes (DEGs) were identified using the Linear Models for Microarray data method and a protein-protein interaction (PPI) network was constructed using data from the Search Tool for the Retrieval of Interacting Genes database followed by module analysis. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis was performed using the Database for Annotation, Visualization and Integrated Discovery. The upstream miRNAs and potential small-molecule drugs were predicted by miRwalk2.0 and Connectivity Map, respectively.ResultsA total of 799 DEGs (449 upregulated and 350 downregulated) were identified. Upregulated DEGs were involved in Cell adhesion molecules (ICAM1, intercellular adhesion molecule 1) and tumor necrosis factor (TNF) signaling pathway (FOS, FBJ osteosarcoma oncogene; ICAM1), while downregulated DEGs participated in PPAR signaling pathway (PPARG, peroxisome proliferator-activated receptor gamma). A PPI network was constructed, in which FOS, ICAM1 and PPARG were ranked as hub genes and PPARG was a transcription factor to regulate other target genes (ICAM1, FOS). Function analysis of two significant modules further demonstrated PPAR signaling pathway was especially important. Furthermore, mmu-miR-130b-3p, mmu-miR-27a-3p, mmu-miR-27b-3p and mmu-miR-721 were predicted to regulate PPARG. Topiramate were speculated to be a potential small-molecule drug to reverse DEGs in AHL.ConclusionsPPAR mediated signaling pathway may be an important mechanism for AHL. Downregulation of the above miRNAs and use of topiramate may be potential treatment strategies for ALH by upregulating PPARG.

Dataset Information

Cumulative lead exposure and age-related hearing loss: the VA Normative Aging Study.

Publications

Cumulative lead exposure and age-related hearing loss: the VA Normative Aging Study.

Similar Datasets

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