Dataset Information

Hearing in 44-45 year olds with m.1555A>G, a genetic mutation predisposing to aminoglycoside-induced deafness: a population based cohort study.

ABSTRACT: Background The mitochondrial DNA mutation m.1555A>G predisposes to permanent idiosyncratic aminoglycoside-induced deafness that is independent of dose. Research suggests that in some families, m.1555A>G may cause non-syndromic deafness, without aminoglycoside exposure, as well as reduced hearing thresholds with age (age-related hearing loss). Objectives To determine whether adults with m.1555A>G have impaired hearing, a factor that would inform the cost-benefit argument for genetic testing prior to aminoglycoside administration. Design Population-based cohort study. Setting UK. Participants Individuals from the British 1958 birth cohort. Measurements Hearing thresholds at 1 and 4 kHz at age 44-45 years; m.1555A>G genotyping. Results 19 of 7350 individuals successfully genotyped had the m.1555A>G mutation, giving a prevalence of 0.26% (95% CI 0.14% to 0.38%) or 1 in 385 (95% CI 1 in 714 to 1 in 263). There was no significant difference in hearing thresholds between those with and without the mutation. Single-nucleotide polymorphism analysis indicated that the mutation has arisen on a number of different mitochondrial haplogroups. Limitations No data were collected on aminoglycoside exposure. For three subjects, hearing thresholds could not be predicted because information required for modelling was missing. Conclusions In this cohort, hearing in those with m.1555A>G is not significantly different from the general population and appears to be preserved at least until 44-45 years of age. Unbiased ascertainment of mutation carriers provides no evidence that this mutation alone causes non-syndromic hearing impairment in the UK. The findings lend weight to arguments for genetic testing for this mutation prior to aminoglycoside administration, as hearing in susceptible individuals is expected to be preserved well into adult life. Since global use of aminoglycosides is likely to increase, development of a rapid test is a priority.

SUBMITTER: Rahman S

PROVIDER: S-EPMC3253422 | biostudies-other | 2012

REPOSITORIES: biostudies-other

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Hearing in 44-45 year olds with m.1555A>G, a genetic mutation predisposing to aminoglycoside-induced deafness: a population based cohort study.

Rahman Shamima S Ecob Russell R Costello Harry H Sweeney Mary G MG Duncan Andrew J AJ Pearce Kerra K Strachan David D Forge Andrew A Davis Adrian A Bitner-Glindzicz Maria M

BMJ open 20120105

Background The mitochondrial DNA mutation m.1555A>G predisposes to permanent idiosyncratic aminoglycoside-induced deafness that is independent of dose. Research suggests that in some families, m.1555A>G may cause non-syndromic deafness, without aminoglycoside exposure, as well as reduced hearing thresholds with age (age-related hearing loss). Objectives To determine whether adults with m.1555A>G have impaired hearing, a factor that would inform the cost-benefit argument for genetic testing prio ...[more]

PMID: 22223843

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Project description:BackgroundSince the mid-1990s, excess mortality has increased markedly for adults aged 25-44 years in the north compared with the south of England. We examined the underlying causes of this excess mortality and the contribution of socioeconomic deprivation.MethodsMortality data from the Office of National Statistics for adults aged 25-44 years were aggregated and compared between England's five most northern versus five most southern government office regions between Jan 1, 1981, and Dec 31, 2016. Poisson regression models, adjusted for age and sex, were used to quantify excess mortality in the north compared with the south by underlying cause of death (accidents, alcohol related, cardiovascular disease and diabetes, drug related, suicide, cancer, and other causes). The role of socioeconomic deprivation, as measured by the 2015 Index of Multiple Deprivation, in explaining the excess and regional variability was also explored.FindingsA mortality divide between the north and south appeared in the mid-1990s and rapidly expanded thereafter for deaths attributed to accidents, alcohol misuse, and drug misuse. In the 2014-16 period, the northern excess was incidence rate ratio (IRR) 1·47 (95% CI 1·39-1·54) for cardiovascular reasons, 2·09 (1·94-2·25) for alcohol misuse, and 1·60 (1·51-1·70) for drug misuse, across both men and women aged 25-44 years. National mortality rates for cardiovascular deaths declined over the study period but a longstanding gap between north and south persisted (from 33·3 [95% CI 31·8-34·8] in 1981 to 15·0 [14·0-15·9] in 2016 in the north vs from 23·5 [22·3-24·8] to 9·9 [9·2-10·5] in the south). Between 2014 and 2016, estimated excess numbers of death in the north versus the south for those aged 25-44 years were 1881 (95% CI 726-2627) for women and 3530 (2216-4511) for men. Socioeconomic deprivation explained up to two-thirds of the excess mortality in the north (IRR for northern effect reduced from 1·15 [95% CI 1·14-1·15; unadjusted] to 1·05 [1·04-1·05; adjusted for Index of Multiple Deprivation]). By 2016, in addition to the persistent north-south gap, mortality rates in London were lower than in all other regions, with IRRs ranging from IRR 1·13 (95% CI 1·12-1·15) for the East England to 1·22 (1·20-1·24) for the North East, even after adjusting for deprivation.InterpretationSharp relative rises in deaths from cardiovascular reasons, alcohol misuse and drug misuse in the north compared with the south seem to have created new health divisions between England's regions. This gap might be due to exacerbation of existing social and health inequalities that have been experienced for many years. These divisions might suggest increasing psychological distress, despair, and risk taking among young and middle-aged adults, particularly outside of London.FundingMedical Research Council and Wellcome Trust.

Dataset Information

Hearing in 44-45 year olds with m.1555A>G, a genetic mutation predisposing to aminoglycoside-induced deafness: a population based cohort study.

Publications

Hearing in 44-45 year olds with m.1555A>G, a genetic mutation predisposing to aminoglycoside-induced deafness: a population based cohort study.

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