title: Estrogen-related receptor gamma and hearing function: evidence of a role in humans and mice.
abstract: Since estrogen is thought to protect pre-menopausal women from age-related hearing loss, we investigated whether variation in estrogen-signalling genes is linked to hearing status in the 1958 British Birth Cohort. This analysis implicated the estrogen-related receptor gamma (ESRRG) gene in determining adult hearing function and was investigated further in a total of 6134 individuals in 3 independent cohorts: (i) the 1958 British Birth Cohort; (ii) a London ARHL case-control cohort; and (iii) a cohort from isolated populations of Italy and Silk Road countries. Evidence of an association between the minor allele of single nucleotide polymorphism (SNP) rs2818964 and hearing status was found in females, but not in males in 2 of these cohorts: p = 0.0058 (London ARHL) and p = 0.0065 (Carlantino, Italy). Furthermore, assessment of hearing in Esrrg knock-out mice revealed a mild 25-dB hearing loss at 5 weeks of age. At 12 weeks, average hearing thresholds in female mice((-/-)) were 15 dB worse than in males((-/-)). Together these data indicate ESRRG plays a role in maintenance of hearing in both humans and mice.
authors.affiliation: UCL Ear Institute, University College London, London, UK.
authors.forename: Lisa S
authors.initials: LS
authors.lastname: Nolan
authors.forename: Hannes
authors.initials: H
authors.lastname: Maier
authors.forename: Irm
authors.initials: I
authors.lastname: Hermans-Borgmeyer
authors.forename: Giorgia
authors.initials: G
authors.lastname: Girotto
authors.forename: Russell
authors.initials: R
authors.lastname: Ecob
authors.forename: Nicola
authors.initials: N
authors.lastname: Pirastu
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Cadge
authors.forename: Christian
authors.initials: C
authors.lastname: Hübner
authors.forename: Paolo
authors.initials: P
authors.lastname: Gasparini
authors.forename: David P
authors.initials: DP
authors.lastname: Strachan
authors.forename: Adrian
authors.initials: A
authors.lastname: Davis
authors.forename: Sally J
authors.initials: SJ
authors.lastname: Dawson
mesh_terms: D000328:Adult; D000818:Animals; D016022:Case-Control Studies; D015331:Cohort Studies; D007758:Ear, Inner / Q000378:metabolism; D005260:Female; D056726:Genetic Association Studies; D006309:Hearing / Q000235:genetics*; D034381:Hearing Loss / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D012737:Sex Factors
chemical_list: C490917:ESRRG protein, human; C490916:Esrrg protein, mouse; D011960:Receptors, Estrogen
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