A rapid method for detection of five known mutations associated with aminoglycoside-induced deafness

Abstract

Background: South Africa has one of the highest incidences of multidrug-resistant tuberculosis (MDR-TB) in the world. Concomitantly, aminoglycosides are commonly used in this country as a treatment against MDR-TB. To date, at least five mutations are known to confer susceptibility to aminoglycoside-induced hearing loss. The aim of the present study was to develop a rapid screening method to determine whether these mutations are present in the South African population.

Aminoglycoside-induced hearing loss in HIV-positive and HIV-negative multidrug-resistant tuberculosis patients

“…The SnapShot technique can detect the 6 known mutations in a single reaction. 5,6 The t-test two-sample assuming unequal variances test was used to calculate the difference in the mean ages between HIV-positive and HIV-negative patients with hearing loss at a 95% confidence interval (CI). The odds ratio (OR) (95% CI) was used to calculate the measure of association of HIV and aminoglycoside-induced hearing loss.…”

“…This study was divided into 2 parts of which the first relates to prevalence of the 6 known aminoglycoside-induced deafness mutations in the MT-RNR1 gene in a cohort of MDR-TB patients. 5,6 Although these data have been published, they are cited where referred to in the text for completeness. The second part involves prospective hearing evaluation.…”

“…This may be associated with a genetic susceptibility caused by the 1555A to G substitution on the mitochondrial 12S rRNA. 5 Genetic predisposition may be predicted by identification of mutations in the MT-RNR1 gene. 5,6 The literature suggests that mitochondrial mutations in the 12S rRNA are rare (0.09% -3.96%), depending on the population studied.…”

“…5 Genetic predisposition may be predicted by identification of mutations in the MT-RNR1 gene. 5,6 The literature suggests that mitochondrial mutations in the 12S rRNA are rare (0.09% -3.96%), depending on the population studied. 7,8 Owing to the rarity of these mutations, genetic predisposition may be unlikely to contribute significantly to the excessive risk of ototoxicity seen in developing countries.…”

Hearing loss in patients on treatment for drug-resistant tuberculosis

“…Recently a number of genes have been identified that show a strong association with aminoglycoside-induced hearing loss [69][70][71][72][73]. These genes are uncommon, however, occurring in ,1% of those tested in a South African population [70].…”