Manuela Baur

Contribution of the N-acetyltransferase 2 polymorphism NAT2*6A to age-related hearing impairment

Background: Age-related hearing impairment (ARHI) is the most common sensory impairment in older people, affecting 50% of those aged 80 years. The proportion of older people is increasing in the general population, and as a consequence, the number of people affected with ARHI is growing. ARHI is a complex disorder, with both environmental and genetic factors contributing to the disease. The first studies to elucidate these genetic factors were recently performed, resulting in the identification of the first two susceptibility genes for ARHI, NAT2 and KCNQ4. Methods: In the present study, the association between ARHI and polymorphisms in genes that contribute to the defence against reactive oxygen species, including GSTT1, GSTM1 and NAT2, was tested. Samples originated from seven different countries and were combined into two test population samples, the general European population and the Finnish population. Two distinct phenotypes for ARHI were studied, Zlow and Zhigh, representing hearing in the low and high frequencies, respectively. Statistical analysis was performed for single polymorphisms (GSTM1, GSTT1, NAT2*5A, NAT2*6A, and NAT2*7A), haplotypes, and gene–environment and gene–gene interactions. Results: We found an association between ARHI and GSTT1 and GSTM1 in the Finnish population sample, and with NAT2*6A in the general European population sample. The latter finding replicates previously published data. Conclusion: As replication is considered the ultimate proof of true associations in the study of complex disorders, this study provides further support for the involvement of NAT2*6A in ARHI.

Genome-wide SNP-based linkage scan identifies a locus on 8q24 for an age-related hearing impairment trait.

Age-related hearing impairment (ARHI), or presbycusis, is a very common multifactorial disorder. Despite the knowledge that genetics play an important role in the etiology of human ARHI as revealed by heritability studies, to date, its precise genetic determinants remain elusive. Here we report the results of a cross-sectional family-based genetic study employing audiometric data. By using principal component analysis, we were able to reduce the dimensionality of this multivariate phenotype while capturing most of the variation and retaining biologically important features of the audiograms. We conducted a genome-wide association as well as a linkage scan with high-density SNP microarrays. Because of the presence of genetic population substructure, association testing was stratified after which evidence was combined by meta-analysis. No association signals reaching genome-wide significance were detected. Linkage analysis identified a linkage peak on 8q24.13-q24.22 for a trait correlated to audiogram shape. The signal reached genome-wide significance, as assessed by simulations. This finding represents the first locus for an ARHI trait.

Functional Analysis of a Novel I71N Mutation in the GJB2 Gene Among Southern Egyptians Causing Autosomal Recessive Hearing Loss

Mutations in GJB2, a gene encoding the gap junction protein connexin 26 (Cx26), are a major cause for inherited and sporadic non-syndromic hearing loss, albeit with highly variable clinical effects. To determine new mutations and their frequencies in a Southern Egyptian population restriction fragment length polymorphism, gene sequencing, and single strand conformational polymorphism revealed only 2 mutations for GJB2: c.35delG and p.I71N. The allelic frequency of the c.35delG mutation was 8.7% (found in 27 out of 310 investigated alleles) resulting in a relatively low carrier frequency (1.6%) in Upper Egypt. The new mutation, a substitution of isoleucin (I) (a non-polar amino acid) by the polar amino acid asparagin (N), was localized within the conserved Cx26 structure. The functional significance of p.I71N was tested by injection of cRNA into Xenopus laevis oocytes. Cx26 hemi-channel activity was measured by depolarization activated conductance in non-coupled oocytes. As a result, the p.I71N mutated channel was non-functional. The study discloses a novel, functionally relevant GJB2 mutation and defines the contribution of Cx26 alterations to the hearing loss in the Southern Egyptian population.

Einfluss exogener Faktoren auf Altersschwerhörigkeit

BACKGROUND Age-related hearing impairment is a complex disorder, the causes for which have been insufficiently studied. Genetic and environmental factors all play a role. METHODS A total of 406 persons aged between 53 and 67 years old were interviewed about various causes and audiometric data were collected. The audiometric pure tone data were adjusted for sex and age and tested for association with exposure to risk factors. RESULTS Significant negative effects of noise exposure, painkillers, overweight, and cardiovascular diseases on hearing loss were found. A positive effect of moderate alcohol consumption could also be shown in the elderly. These results suggest that a healthy lifestyle can positively affect age-related hearing impairment.ZusammenfassungHintergrundAltersschwerhörigkeit ist eine komplexe Erkrankung, deren Ursachen nur unzureichend erforscht sind. Sowohl genetische als auch Umweltfaktoren spielen eine Rolle.MethodenEs wurden 406 Personen im Alter von 53–67 Jahren zu verschiedenen Ursachen befragt und audiometrisch untersucht. Die audiometrischen Daten wurden nach Geschlecht und Alter bereinigt und auf Assoziationen mit einer Risikofaktorexposition untersucht.ErgebnisseEs konnten signifikante negative Effekte von Lärmexposition, Schmerzmitteln, Übergewicht und Herz-Kreislauf-Erkrankungen auf das Gehör gezeigt werden. Moderater Alkoholgenuss ist mit einem besseren Hörvermögen im Alter assoziiert. Diese Ergebnisse deuten an, dass ein gesunder Lebensstil sich positiv auf Altersschwerhörigkeit auswirken kann.AbstractBackgroundAge-related hearing impairment is a complex disorder, the causes for which have been insufficiently studied. Genetic and environmental factors all play a role.MethodsA total of 406 persons aged between 53 and 67 years old were interviewed about various causes and audiometric data were collected. The audiometric pure tone data were adjusted for sex and age and tested for association with exposure to risk factors.ResultsSignificant negative effects of noise exposure, painkillers, overweight, and cardiovascular diseases on hearing loss were found. A positive effect of moderate alcohol consumption could also be shown in the elderly. These results suggest that a healthy lifestyle can positively affect age-related hearing impairment.

[Influence of exogenic factors on age-related hearing impairment].

BACKGROUND Age-related hearing impairment is a complex disorder, the causes for which have been insufficiently studied. Genetic and environmental factors all play a role. METHODS A total of 406 persons aged between 53 and 67 years old were interviewed about various causes and audiometric data were collected. The audiometric pure tone data were adjusted for sex and age and tested for association with exposure to risk factors. RESULTS Significant negative effects of noise exposure, painkillers, overweight, and cardiovascular diseases on hearing loss were found. A positive effect of moderate alcohol consumption could also be shown in the elderly. These results suggest that a healthy lifestyle can positively affect age-related hearing impairment.ZusammenfassungHintergrundAltersschwerhörigkeit ist eine komplexe Erkrankung, deren Ursachen nur unzureichend erforscht sind. Sowohl genetische als auch Umweltfaktoren spielen eine Rolle.MethodenEs wurden 406 Personen im Alter von 53–67 Jahren zu verschiedenen Ursachen befragt und audiometrisch untersucht. Die audiometrischen Daten wurden nach Geschlecht und Alter bereinigt und auf Assoziationen mit einer Risikofaktorexposition untersucht.ErgebnisseEs konnten signifikante negative Effekte von Lärmexposition, Schmerzmitteln, Übergewicht und Herz-Kreislauf-Erkrankungen auf das Gehör gezeigt werden. Moderater Alkoholgenuss ist mit einem besseren Hörvermögen im Alter assoziiert. Diese Ergebnisse deuten an, dass ein gesunder Lebensstil sich positiv auf Altersschwerhörigkeit auswirken kann.AbstractBackgroundAge-related hearing impairment is a complex disorder, the causes for which have been insufficiently studied. Genetic and environmental factors all play a role.MethodsA total of 406 persons aged between 53 and 67 years old were interviewed about various causes and audiometric data were collected. The audiometric pure tone data were adjusted for sex and age and tested for association with exposure to risk factors.ResultsSignificant negative effects of noise exposure, painkillers, overweight, and cardiovascular diseases on hearing loss were found. A positive effect of moderate alcohol consumption could also be shown in the elderly. These results suggest that a healthy lifestyle can positively affect age-related hearing impairment.

Impact of Hereditary Hemorrhagic Teleangiectasia on Quality of Life

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominantly inherited disorder of the fibrovascular tissue. The most common symptoms are recurrent nose bleeds and multiple mucocutaneous telangiectases. Arteriovenous malformations (AVMs) are less obvious. Because there is no permanent cure available, patients often suffer from mental stress. Several studies have been performed to assess the quality of life (QoL) of HHT patients. These studies showed that HHT patients rated bodily pain lower than the general population but altogether they had lower health-related QoL.

Einfluss exogener Faktoren auf Altersschwerhörigkeit@@@Influence of exogenic factors on age-related hearing impairment

BACKGROUND Age-related hearing impairment is a complex disorder, the causes for which have been insufficiently studied. Genetic and environmental factors all play a role. METHODS A total of 406 persons aged between 53 and 67 years old were interviewed about various causes and audiometric data were collected. The audiometric pure tone data were adjusted for sex and age and tested for association with exposure to risk factors. RESULTS Significant negative effects of noise exposure, painkillers, overweight, and cardiovascular diseases on hearing loss were found. A positive effect of moderate alcohol consumption could also be shown in the elderly. These results suggest that a healthy lifestyle can positively affect age-related hearing impairment.ZusammenfassungHintergrundAltersschwerhörigkeit ist eine komplexe Erkrankung, deren Ursachen nur unzureichend erforscht sind. Sowohl genetische als auch Umweltfaktoren spielen eine Rolle.MethodenEs wurden 406 Personen im Alter von 53–67 Jahren zu verschiedenen Ursachen befragt und audiometrisch untersucht. Die audiometrischen Daten wurden nach Geschlecht und Alter bereinigt und auf Assoziationen mit einer Risikofaktorexposition untersucht.ErgebnisseEs konnten signifikante negative Effekte von Lärmexposition, Schmerzmitteln, Übergewicht und Herz-Kreislauf-Erkrankungen auf das Gehör gezeigt werden. Moderater Alkoholgenuss ist mit einem besseren Hörvermögen im Alter assoziiert. Diese Ergebnisse deuten an, dass ein gesunder Lebensstil sich positiv auf Altersschwerhörigkeit auswirken kann.AbstractBackgroundAge-related hearing impairment is a complex disorder, the causes for which have been insufficiently studied. Genetic and environmental factors all play a role.MethodsA total of 406 persons aged between 53 and 67 years old were interviewed about various causes and audiometric data were collected. The audiometric pure tone data were adjusted for sex and age and tested for association with exposure to risk factors.ResultsSignificant negative effects of noise exposure, painkillers, overweight, and cardiovascular diseases on hearing loss were found. A positive effect of moderate alcohol consumption could also be shown in the elderly. These results suggest that a healthy lifestyle can positively affect age-related hearing impairment.