Per-Inge Carlsson

The influence of genetic variation in oxidative stress genes on human noise susceptibility

Noise induced hearing loss (NIHL) is a complex disease caused by an interaction between genetic and environmental factors. Damage in the cochlea as a result of noise exposure appears to be mediated by reactive oxygen species (ROS). To investigate whether genetic variation in the human protective antioxidant system is associated with high or low susceptibility to NIHL, genetic polymorphisms derived from genes involved in the oxidative stress response were analysed in the 10% most susceptible and 10% most resistant extremes of 1200 Swedish noise-exposed workers. The genetic polymorphisms included 2 deletion polymorphisms for the GSTM1 and GSTT1 gene, and 14 SNPs derived from the CAT, SOD, GPX, GSR and GSTP1 genes. No significant differences were found between susceptible and resistant groups, providing no support for a major role of genetic variation of antioxidant enzymes in the susceptibility to NIHL.

Variations in HSP70 genes associated with noise-induced hearing loss in two independent populations

Noise-induced hearing loss (NIHL) is one of the most important occupational health hazards. Millions of people worldwide are exposed daily to harmful levels of noise. NIHL is a complex disease resulting from an interaction between genetic and environmental factors. Although the environmental risk factors have been studied extensively, little is known about the genetic factors. Heat-shock proteins (HSPs) are induced after exposure to severe noise. When first induced by exposure to moderate sound levels, they can protect the ear from damage from excessive noise exposure. This protection is highly variable between individuals. An association of HSP70 genes with NIHL has been described by Yang et al (2006) in a Chinese sample set of noise-exposed workers. In this study, three polymorphisms (rs1043618, rs1061581 and rs2227956) in HSP70-1, HSP70-2 and HSP70-hom, respectively, were genotyped in 206 Swedish and 238 Polish DNA samples of noise-exposed subjects and analyzed. One SNP, rs2227956 in HSP70-hom, resulted in a significant association with NIHL in both sample sets. In addition, rs1043618 and rs1061581 were significant in the Swedish sample set. Analysis of the haplotypes composed of the three SNPs revealed significant associations between NIHL and haplotype GAC in both sample sets and with haplotype CGT in the Swedish sample set. In conclusion, this study replicated the association of HSP70 genes with NIHL in a second and third independent noise-exposed sample set, hereby adding to the evidence that HSP70 genes may be NIHL susceptibility genes.

Candidate Gene Association Study for Noise-induced Hearing Loss in Two Independent Noise-exposed Populations

Millions of people are daily exposed to high levels of noise. Consequently, noise‐induced hearing loss (NIHL) is one of the most important occupational health hazards worldwide. In this study, we performed an association study for NIHL based on a candidate gene approach. 644 Single Nucleotide Polymorphisms (SNPs) in 53 candidate genes were analyzed in two independent NIHL sample sets, a Swedish set and part of a Polish set. Eight SNPs with promising results were selected and analysed in the remaining part of the Polish samples. One SNP in PCDH15 (rs7095441), resulted in significant associations in both sample sets while two SNPs in MYH14 (rs667907 and rs588035), resulted in significant associations in the Polish sample set and significant interactions with noise exposure level in the Swedish sample set. Calculation of odds ratios revealed a significant association of rs588035 with NIHL in the Swedish high noise exposure level group. Our studies suggest that PCDH15 and MYH14 may be NIHL susceptibility genes, but further replication in independent sample sets is mandatory.

Analysis of Gene Polymorphisms Associated with K+ Ion Circulation in the Inner Ear of Patients Susceptible and Resistant to Noise‐induced Hearing Loss

Noise‐induced hearing loss (NIHL) is one of the leading occupational health risks in industrialized countries. It results from an interaction between environmental and genetic factors, however the nature of the genetic factors contributing to NIHL has not yet been clarified. Here, we investigated whether genetic variations in 10 genes putatively involved in the potassium recycling pathway in the inner ear may influence susceptibility to noise. 99 SNPs were genotyped in Polish noise‐exposed workers, categorized into susceptible and resistant subjects. The most interesting results were obtained for KCNE1 and KCNQ4 as we replicated associations that were previously reported in a Swedish sample set, hence confirming that they are NIHL susceptibility genes. Additionally we report significant associations in GJB1, GJB2, GJB4, KCNJ10 and KCNQ1, however due to the lack of replication in the Swedish sample set, these results should be seen as suggestive.

Quality of life, psychosocial consequences, and audiological rehabilitation after sudden sensorineural hearing loss.

Abstract Objective: Sudden sensorineural hearing loss (SSHL) is characterized by a rapid loss of hearing, most often of cochlear origin. Very little attention has been paid in the literature to quality of life (QoL), psychosocial consequences and audiological rehabilitation after SSHL. Design: We studied how level of hearing loss, hearing recovery, tinnitus and vertigo affect QoL after SSHL and the psychosocial consequences of SSHL in terms of sick leave. Furthermore, the audiological rehabilitation given to patients in connection with SSHL and the benefit of the rehabilitation were studied. Study Sample: Three hundred and sixty-nine (369) patients with SSHL were analysed in the present study. Results: Annoying tinnitus and remaining vertigo after SSHL were the strongest predictors of negative effects on QoL. Conclusions: The study indicates that patients with SSHL require extended audiological rehabilitation including a multi-disciplinary rehabilitation approach (medical, social and psychological) to cope with the complex issues that can arise after SSHL. Sumario Objetivo: La pérdida auditiva sensorineural súbita (SSHL) se caracteriza por una rápida pérdida de la audición, más a menudo de origen coclear. Se ha prestado muy poca atención en la literatura a la calidad de vida (QoL), a las consecuencia psicosociales y la rehabilitación audiológica después de una SSHL. Diseño: Estudiamos cómo los niveles de pérdida auditiva, la recuperación de la audición, el acúfeno y el vértigo, afectan la QoL luego de una SSHL, y las consecuencia psicosociales de la SSHL en términos de incapacidades laborales. Más aún, se estudió la rehabilitación audiológica dada a estos pacientes en conexión con la SSHL, y los beneficios de la rehabilitación. Muestra De Estudio: Trescientos sesenta y nueve (369) pacientes con SSHL fueron analizados en el presente estudio. Resultados: Un acúfeno fastidioso y un vértigo remanente luego de la SSHL, fueron los vaticinadores más fuertes de los efectos negativos sobre la QoL. Conclusiones: El estudio indica que los pacientes con SSHL demandan una rehabilitación audiológica extendida, incluyendo un enfoque de rehabilitación multi-disciplinario (médico, social y psicológico), sobrellevar los complejos asuntos que puede surgir luego de una SSHL.

Congenital cytomegalovirus infection - a common cause of hearing loss of unknown aetiology.

Aim:  The aim of this study was to investigate the role of congenital cytomegalovirus (CMV) infection as a cause of various types of sensorineural hearing loss (SNHL) in a group of nonsyndromic children with otherwise unknown aetiology of hearing loss. Furthermore, the occurrence of combined congenital CMV infection and connexin 26 (Cx26) mutations was investigated.

Variability in noise susceptibility in a Swedish population: the role of 35delG mutation in the connexin 26 (GJB2) gene

Although it seems that genetic factors can influence individual susceptibility to noise, still very little is known about the genes or the mechanisms involved. The connexin 26 (Cx26) (GJB2) gene is of particular interest to study in relation to noise, since the gene encodes the gap junction protein Cx26. Noise has a metabolic and mechanical effect on the inner ear and may, therefore, interfere with gap junction channels. In order to investigate whether abnormally high susceptibility to noise induced hearing loss (NIHL) in humans is associated with the common 35delG mutation in the Cx26 gene, 1200 noise‐exposed workers were investigated in Sweden. Using a selection procedure based on audiometric analysis, noise exposure data and questionnaires, noise‐exposed workers were divided into two categories: noise susceptible and noise resistant. There was a correspondence in noise susceptibility between this noise‐exposed population and the international reference ISO Standard 1999. Blood samples were drawn from 245 highly selected male subjects (103 noise susceptible, 112 noise resistant and 30 randomized cases), and genomic DNA was analysed with respect to the Cx26 35delG mutation. The incidence of 35delG carriers among this cohort was determined by multiplex, allele‐specific PCR. Two of the 245 subjects (0.8% ‐ [95% confidence interval 0.1–2.9]) were found to be heterozygous carriers of the 35delG mutation, while the remaining 243 subjects were all non‐carriers. Both the heterozygous carriers were found in the noise susceptible group. Statistical evaluation of the results demonstrated no significant difference in carrier incidence between the noise susceptible and noise resistant individuals in our Swedish noise‐exposed population. In conclusion, there was no support for a major role of Cx26 35delG mutation in explaining the variability in noise susceptibility in this Swedish population.

Severe to profound hearing impairment: quality of life, psychosocial consequences and audiological rehabilitation

Abstract Purpose: To study the quality of life (QoL) and psychosocial consequences in terms of sick leave and audiological rehabilitation given to patients with severe to profound hearing impairment. Method: A retrospective study of data on 2319 patients with severe to profound hearing impairment in The Swedish Quality Register of Otorhinolaryngology, followed by a posted questionnaire including The Hospital Anxiety and Depression Scale (HADS). Results: The results indicate greater levels of anxiety and depression among patients with severe or profound hearing impairment than in the general population, and annoying tinnitus and vertigo had strong negative effects on QoL. The proportion of sick leave differed between the studied dimensions in the study. The proportion of patients who received extended audiological rehabilitation was 38% in the present study. Conclusions: Treatment focused on anxiety, depression, tinnitus and vertigo must be given early in the rehabilitation process in patients with severe or profound hearing impairment. Because sick leave differs greatly within this group of patients, collaboration with the regional Social Insurance Agency is crucial part of the rehabilitation. The study also shows that presently, only a small proportion of patients in Sweden with severe to profound hearing impairment receive extended audiological rehabilitation. Implications for Rehabilitation Greater levels of anxiety and depression have been found among patients with severe or profound hearing impairment than in the general population, and annoying tinnitus and vertigo have strong negative effects on QoL in this group of patients. Only a small proportion of patients with severe to profound hearing impairment receive extended audiological rehabilitation today, including medical, technical and psychosocial efforts. Extended audiological rehabilitation focused on anxiety, depression, tinnitus and vertigo must be given, together with technical rehabilitation, early in the rehabilitation process in patients with severe or profound hearing impairment.

GJB2 (Connexin 26) gene mutations among hearing-impaired persons in a Swedish cohort

Abstract Conclusion: The most common mutation in the Swedish population was Connexin 26 (C×26) 35delG, which indicates that the percentage of Swedish persons with C×26 mutations and polymorphisms in the GJB2 gene among non-syndromic hearing-impaired (HI) persons is comparable to the rest of Europe. The results strongly support a Swedish policy to offer all children with diagnosed hearing impairment genetic tests for the C×26 35delG mutation. Objectives: The aim of the present study was to search for mutations in the GBJ2 gene among Swedish persons with non-syndromic hearing impairment to further clarify how common these mutations are in Sweden, one of the northernmost countries in Europe. Methods: Seventy-nine patients with non-syndromic hearing impairment participated in the study. For 87% of the participants, a pure tone audiogram showed a severe or profound hearing impairment. Dried blood spots on filter paper, taken at 3–5 days of age in the Swedish nationwide neonatal screening programme for congenital disorders and saved in a biobank, were used for the molecular genetic analyses. Results: The total number of subjects with one or two pathologic mutations or a mutation of unknown consequence found in the GJB2 gene was 28 of 79 (35%). Nineteen (19) persons (24%) were homozygotes for the 35delG mutation.

MARITAL STATUS AND BIRTHRATE OF DEAF PEOPLE IN TWO SWEDISH COUNTIES: THE IMPACT OF SOCIAL ENVIRONMENT IN TERMS OF DEAF COMMUNITY

Deafness affects many social interactions. The impact of deafness depends on several factors, e.g., the type of social environment in terms of the particular Deaf community a person lives in. The authors recorded the birthrate and the proportions of married and divorced people among deaf people in two Swedish counties: Narke, which had a strong Deaf community, and Varmland, whose Deaf community was weak. In both counties, the authors found that deafness was associated with low marriage rates and low birthrates. Further, in Narke, 99% of the people in the sample were married to another deaf person; only 10% were in Varmland. In Narke, the divorce rate among deaf people was about the same as that of the reference population (i.e., the countys marriage-age population). In Varmland, deaf people had a relatively low divorce rate. The findings are discussed from medical and social perspectives.