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|Title:||Genes and lifestyle in normal hearing function and age-related hearing loss||Authors:||Girotto, Giorgia||Supervisore/Tutore:||Gasparini, Paolo||Issue Date:||9-Apr-2013||Publisher:||Università degli studi di Trieste||Abstract:||
The auditory system is a complex machinery, constituted by many
molecules involving hair cells, cochlear neurons, the stria vascularis, and
combinations thereof. The analysis of complex genetic traits/diseases
such as normal hearing function and Age-Related Hearing Loss has long
been an enigma of genetic biology, whether in the animal or in medical
sciences. In particular, Age-Related Hearing Loss is the most prevalent
sensory impairment in the elderly affecting 30% of people aged over 60.
The disease is not directly life threatening but it contributes to loss of
autonomy and is associated with anxiety, depression, and cognitive
decline largely compromising the quality of life.
Until now, only few genes are known to contribute to variability of normal
hearing function and Age-Related Hearing Loss. In both cases interactions
between lifestyle and environmental determinants as well as several
molecular and cellular basis and pathways should be taken into account.
The main aim of the thesis is the understanding of the molecular bases of
variation of normal hearing function and Age-Related Hearing Loss using:
a) Genome Wide Association Studies to identify new genes/loci, b)
immunohistochemistry to evaluate their expression in the mouse cochlea
and c) epidemiological studies to identify environmental/lifestyle factors.
Genome-Wide Association studies and the following Meta-analysis have
been carried out on 3815 people coming from isolated villages located in
Italy, Croatia, Caucasus and central Asia recruited within the International
Consortium G-EAR leading to the identification of 3 loci (rs614171 on
chromosome 13, rs3786724 on chromosome 19, rs11711388 on
chromosome 3) with p-value≈1*10-8, 26 loci with p-value ≈1*10-7 and many
others with high p-value.
23 genes have been then chosen for evaluation using expression studies
in wildtype mice by immunohistochemistry and confocal microscopy. Five
of them (Arsg, Slc16a6, Dclk1, Gabrg3, Csmd1) display strikingly specific
expression in the cochlea and additional eight (Ptprd, Grm8,
Kiaa056/GlyBP, Evi5, Irg1, Rimbp2, Ank2, Cdh13) show expression in
multiple cell types of the cochlea.
As regards environmental/lifestyle factors, the epidemiological analysis
revealed that coffee consumption (coffee yes vs. no) and coffee intake
(cups/day) displayed a significant association with better hearing function
in four out of ten populations investigated. In particular, coffee drinking
was associated at low and high frequencies (lowest p-value=0.006) while
the intake only at high frequency (lowest p-value=0.003). Moreover, a
statistical significant association between ARHL and education level was
detected (lowest p-value=0.0003) confirming previously reported data.
|Ciclo di dottorato:||XXV Ciclo||metadata.dc.subject.classification:||SCUOLA DI DOTTORATO DI RICERCA IN SCIENZE DELLA RIPRODUZIONE - indirizzo GENETICO MOLECOLARE||Description:||
|Keywords:||normal hearing function,; GWAS; expression studies; Age-Related Hearing Loss||Type:||Doctoral||Language:||en||Settore scientifico-disciplinare:||MED/03 GENETICA MEDICA||NBN:||urn:nbn:it:units-9965|
|Appears in Collections:||Scienze mediche|
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