Contribution of adiponectin and its type 1 receptor to age-related hearing impairment.
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.
Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan; Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan.
Chen-Chi
CC
Wu
Institute of Epidemiology and Preventive Medicine, National Taiwan University College of Public Health, Taipei, Taiwan.
Ching-Hui
CH
Tsai
Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan.
Ying-Chang
YC
Lu
Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan.
Hsiao-Chun
HC
Lin
Department of Otolaryngology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan; School of Medicine, Tzu Chi University, Hualien, Taiwan.
Juen-Haur
JH
Hwang
Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Medical Genomics and Proteomics, National Taiwan University College of Medicine, Taipei, Taiwan.
Yin-Hung
YH
Lin
Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
Wei-Shiung
WS
Yang
Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
Pei-Jer
PJ
Chen
Health Management Center, National Taiwan University Hospital, Taipei, Taiwan.
Wei-Chih
WC
Liao
Institute of Epidemiology and Preventive Medicine, National Taiwan University College of Public Health, Taipei, Taiwan; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan. Electronic address: leolee@ntu.edu.tw.
Yungling Leo
YL
Lee
Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan. Electronic address: liuent@ntu.edu.tw.
Tien-Chen
TC
Liu
Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan; Department of Otolaryngology, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan. Electronic address: cjhsu@ntu.edu.tw.
Chuan-Jen
CJ
Hsu
D052242:Adiponectin / Q000097:blood / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D003051:Cochlea / Q000166:cytology / Q000473:pathology; D007758:Ear, Inner / Q000378:metabolism; D004843:Epistasis, Genetic; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D034381:Hearing Loss / Q000235:genetics*; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D054419:Receptors, Adiponectin / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
C499918:ADIPOQ protein, human; C475418:ADIPOR1 protein, human; D052242:Adiponectin; C499919:Adipoq protein, mouse; D054419:Receptors, Adiponectin
ADIPOR1; Adiponectin; Age-related hearing impairment