Contribution of adiponectin and its type 1 receptor to age-related hearing impairment
Journal
Neurobiology of Aging
Journal Volume
36
Journal Issue
6
Pages
2085-2093
Date Issued
2015
Author(s)
Tsai C.-H.
Lu Y.-C.
Lin H.-C.
Hwang J.-H.
Lin Y.-H.
Lee Y.L.
Hsu C.-J.
Abstract
Age-related hearing impairment (ARHI) is a complex neurodegenerative disorder caused by a combination of environmental and genetic factors. We have reported previously that obesity increases the risk for ARHI, and that plasma levels of adiponectin are associated with ARHI. In the present study, we further explored the role of adiponectin in the pathophysiology of ARHI by investigating the genotypes of ADIPOQ and ADIPOR1, the genes of adiponectin and its type 1 receptor, respectively. A total of 1682 volunteers were enrolled, and their audiological phenotypes were determined according to the z scores converted from their original frequency-specific hearing thresholds. A total of 9 tag-single nucleotide polymorphisms (tagSNPs) in ADIPOQ and 4 tagSNPs in ADIPOR1 were genotyped, and the genotypes were correlated to the audiological phenotypes under the assumption of various inheritance models. Significant associations were identified between certain ADIPOQ tagSNPs and z scores under dominant, codominant, or additive models, whereas no association was identified between ADIPOR1 tagSNPs and z scores. The associations between ADIPOQ tagSNPs and z scores appear to exist only in subjects with specific ADIPOR1 genotypes, indicating an interaction between adiponectin and AdipoR1. Measurement of plasma adiponectin in 736 subjects revealed that ADIPOQ genotypes might exert their effects on hearing levels via modulation of plasma adiponectin levels. Subsequently, we confirmed the expression of AdipoR1 in the inner ear of mice, and demonstrated antiapoptotic effects of adiponectin in cochlear explant cultures. These results provide insights into the physiological function and potential clinical implications of adiponectin against ARHI. ? 2015 Elsevier Inc.
SDGs
Other Subjects
adiponectin; adiponectin receptor 1; adiponectin; adiponectin receptor; ADIPOQ protein, human; Adipoq protein, mouse; ADIPOR1 protein, human; ADIPOQ gene; ADIPOR1 gene; adult; age related hearing impairment; Article; auditory threshold; female; gene; gene expression; gene identification; genotype; hearing impairment; human; major clinical study; male; pathophysiology; priority journal; protein blood level; single nucleotide polymorphism; aged; aging; animal; apoptosis; blood; cell culture; cochlea; cytology; drug effects; epistasis; genetic association; genetics; hearing impairment; inner ear; metabolism; middle aged; mouse; pathology; physiology; very elderly; Adiponectin; Adult; Aged; Aged, 80 and over; Aging; Animals; Apoptosis; Cells, Cultured; Cochlea; Ear, Inner; Epistasis, Genetic; Female; Genetic Association Studies; Genotype; Hearing Loss; Humans; Male; Mice; Middle Aged; Polymorphism, Single Nucleotide; Receptors, Adiponectin
Publisher
Elsevier Inc.
Type
journal article