Susceptibilidade genética e impacto social da surdez associada à idade

Susceptibilidade genética e impacto social da surdez associada à idade

Presbycusis or age-related hearing loss (ARHL) is the most common sensory impairment in the elderly, often leading to social isolation and diminished quality of life, and affecting millions of people worldwide. ARHL is a multifaceted common phenomenon, with a broad spectrum of causes, bot h environment al and genetic, and cognitive and psychosocial consequences. Genetic susceptibility associated with presbycusis implies that ARHL isn't an inevitable condition, but a complex disease with possible treatment and prevent ion. This assumption, combined with the few information still existing about the epidemiology of hearing loss in elderly people and about the manifestation of several etiological factors for this condition, justifies the relevance of the project here proposed.
Previous studies found an association between presbycusis and some genes involved in hereditary deafness - GJB2 and KCNQ4 - or in oxidative metabolism - NAT2, GSTM1, GSTT1, GRHL2 and GRM7. I n t he mitochondrial DNA, t he 4977bp deletion, and haplogroups U and K, have also been associated with presbycusis.
The increase of the elderly population worldwide due to increased life expectancy, highlight s the importance of studies on presbycusis.
The general aim of this study is the identification of epidemiological and etiological factors associated with ARHL in a sample of elder Portuguese individuals (n≈ 1000) through the establishment of statistically significant genotype - phenotype correlations found in this sample. Specific objectives will include:

a) Hearing screening by perform epidemiological and etiological studies of the individuals from our sample;
b) Genetic screening, by determining the prevalence in the Portuguese elderly population of variant s in genes/loci previously associated with ARHL in other populations;
c) Phenotype-genotype correlation by studying the association between the genetic variant s found and the epidemiological and etiological factors identified on the elderly individuals with presbycusis;
d) Study of the social dimensions of presbycusis, and the sociodemographic description of the elderly individuals of the sample by applying a questionnaire that also considers the processes of aging, uses of the time, occupations, and social networks.

 

 

Estatuto: 
Entidade participante
Financiado: 
Sim
Entidades: 
Fundação para a Ciência e Tecnologia
Rede: 
Principal Contractor: Fundação da Faculdade de Ciências (FFC/FC/UL) Participating Institutions: Centro Hospitalar e Universitário de Coimbra, E.P.E. (CHUC), Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa (FCT/UNL), Instituto de Ciências Sociais (ICS/ULisboa) and Instituto Politécnico de Setúbal (IPSetúbal)
Keywords: 

Genetic risk, Age-related hearing impairment, Social isolation

Presbycusis or age-related hearing loss (ARHL) is the most common sensory impairment in the elderly, often leading to social isolation and diminished quality of life, and affecting millions of people worldwide. ARHL is a multifaceted common phenomenon, with a broad spectrum of causes, bot h environment al and genetic, and cognitive and psychosocial consequences. Genetic susceptibility associated with presbycusis implies that ARHL isn't an inevitable condition, but a complex disease with possible treatment and prevent ion. This assumption, combined with the few information still existing about the epidemiology of hearing loss in elderly people and about the manifestation of several etiological factors for this condition, justifies the relevance of the project here proposed.
Previous studies found an association between presbycusis and some genes involved in hereditary deafness - GJB2 and KCNQ4 - or in oxidative metabolism - NAT2, GSTM1, GSTT1, GRHL2 and GRM7. I n t he mitochondrial DNA, t he 4977bp deletion, and haplogroups U and K, have also been associated with presbycusis.
The increase of the elderly population worldwide due to increased life expectancy, highlight s the importance of studies on presbycusis.
The general aim of this study is the identification of epidemiological and etiological factors associated with ARHL in a sample of elder Portuguese individuals (n≈ 1000) through the establishment of statistically significant genotype - phenotype correlations found in this sample. Specific objectives will include:

a) Hearing screening by perform epidemiological and etiological studies of the individuals from our sample;
b) Genetic screening, by determining the prevalence in the Portuguese elderly population of variant s in genes/loci previously associated with ARHL in other populations;
c) Phenotype-genotype correlation by studying the association between the genetic variant s found and the epidemiological and etiological factors identified on the elderly individuals with presbycusis;
d) Study of the social dimensions of presbycusis, and the sociodemographic description of the elderly individuals of the sample by applying a questionnaire that also considers the processes of aging, uses of the time, occupations, and social networks.

 

 

Objectivos: 
The present project will contribute to improving the knowledge on the epidemiology of presbycusis, and on genotype - phenotype correlations concerning ARHL in the Portuguese elderly population. It will also measure the social dimensions associated to this condition in our sample. We also aim to contribute to better counseling and to the definition of the best therapeutic approaches and prevent ion, thus contributing for a hearing healthcare culture regarding elderly people and t o a better quality of life of the elder Portuguese population, having in mind too that 2012 was declared by the European Parliament as the ‘European Year for Active Ageing and Solidarity between Generations'.
State of the art: 
Presbycusis, or aging-related hearing loss (ARHL), is the most com m on sensory impairment in the elderly, affecting approximately 60% of all individuals over 65 years in the world. It is characterized by a bilateral progressive hearing loss starting in the high frequencies and results from degeneration of the cochlear structures in the inner ear. It is usually accompanied by a decrease in<br />communication skills, being referred as &quot;social deafness&quot; since it has a negative influence on the elders' quality of life and can lead to social isolation, depression and anxiety. In Portugal, according to our own studies, older people (especially over 65) are less likely to participate in social activities and more likely to suffer from social isolation and frequently from loneliness. In most cases, hearing<br />disabilities in adults take a long time to develop, being a progressive process in which the diminished ability to hear and to communicate is frustrating in and of itself, but the strong association of hearing disability with depression and functional decline adds furt her t o t he burden on individuals who are hearing - impaired. Presbycusis is nowadays a major health concern in industrialized countries due to extended life expectancy. As a consequence a large increase of ARHL in the elderly population has been observed with an even greater impact on their health and quality of life. However, a large number of underdetected and underdiagnosed hearing disabilities in older adult s still exist, and there is a lack of internationally accepted guidelines, protocols and legislation. Novel strategies should be explored to make screening for hearing disabilities part of routine care. Also necessary is a better understanding of the etiological and epidemiological factors underlying ARHL. Only by an accurate etiological assessment can further strategies for follow-up and intervention be significantly improved. ARHL is a multifactorial disease that is thought to be precipitated by several factors both environmental (noise exposure, trauma, vascular damage, malnutrition, tobacco smoking, alcohol abuse) and genetic, these ones dictating a genetic susceptibility (or risk factor) to presbycusis. Logically, the candidate genes that might be associated with presbycusis were genes already associated with hereditary deafness or with processes intrinsic to aging. Certain genes/loci<br />responsible for nonsyndromic forms of deafness as KCNQ4, GJB2, DFNA2, DFNA5, DFNA8 and DFNA12 have been investigated in ARHL individuals and in some of these genes significant SNPs were found. As regards the physiological processes of aging, oxidative stress appears as the most significant, since it mainly affects tissues with high energy needs, such as the cochlear structures. In<br />parallel, mitochondrial DNA (mt DNA) dam age accumulates preferentially in tissues such as the inner ear. As a matter of fact, significant associations have already been found between presbycusis and: (1) the mt DNA 4977bp deletion, ( 2) mitochondrial haplogroups U and K, and ( 3) NAT2* 6A haplotype on N- acetyltransferase 2 gene, import ant for the oxidative balance in the cell. Also<br />in the glutathione S- transferases group of antioxidant enzymes, deletions in the GSTM1 and GSTT1 genes have been associated with an increased risk for the development of presbycusis. Recently, two genome-wide multicenter association studies, performed on ARHL samples from seven European countries, identified a highly significant SNP in the GRHL2 gene, which encodes a transcription fact or<br />expressed in the cells lining the cochlear duct , and a highly significant and replicated SNP in the GRM7 gene, coding for a m et abotropic glutamate receptor. These findings provide evidence that variation in either GRHL2 or GRM7 is associated with ARHL.<br />Despite the promising results obtained in these different studies, little is yet known about what triggers presbycusis. It is possible that certain environmental factors are harmful only in certain individual's genetic background. As such, presbycusis may be a prevent able condition, and so personalized methods can be designed for future treatment and/ or prevention depending on the individual 's genetic susceptibilit y profile. In this study, we aim to enhance the know ledge on presbiacusys' genetic factors and other relevant etiological factors such as cardiovascular diseases, noise exposure, ototoxicity, smoking, diabetes, gender and diet , assessed through clinical, audiologic and audiogram analysis. All this factors, other than genetics factors, and data on prevalence of hearing disabilities and demographic history could provide reliable data for screening programs of hearing and thus possibly contribute to future therapeutic and preventive approaches that would lead to a better quality of life in the elderly populations worldwide.<p>&nbsp;</p>
Parceria: 
Rede Nacional
Cláudia Andrade
Graça Fialho
João Moura
Joana Chora
Jorge Martins
Maria O'Neill
Marta Arguello
João Goyri O'Neill
Coordenador Geral 
Helena Caria
Coordenador 
Data Inicio: 
01/04/2013
Data Fim: 
31/03/2015
Concluído