Functional Polymorphism of MMP9 and BDNF as Potential Biomarker of Auditory Neuroplasticity in Prelingual Deafness Treatment With Cochlear Implantation—A Retrospective Cohort Analysis

Abstract

Genetic biomarkers of neuroplasticity in deaf children treated with cochlear implantation (CI) might facilitate their clinical management, especially giving them better chances of developing proficient spoken language. We investigated whether carrying certain variants of the genes encoding matrix metalloproteinase MMP9 and neurotrophin brain-derived neurotrophic factor (BDNF), involved in synaptic plasticity, can be taken as prognostic markers of how well auditory skills might be acquired. Association analysis of functional MMP9 rs3918242 and BDNF rs6265 variants and the child’s auditory development measured at CI activation and 1, 5, 9, 14, and 24\u2009months post CI activation with LittlEARS Questionnaire (LEAQ) was conducted in a group of 100 children diagnosed with DFNB1-related deafness, unilaterally implanted before the age of 2\u2009years. Statistical analysis in the subgroup implanted after 1\u2009year of life (n\u2009=\u200953) showed significant association between MMP9 rs3918242 and LEAQ scores at 1\u2009month (p\u2009=\u2009.01), at 5\u2009months (p\u2009=\u2009.01), at 9\u2009months (p\u2009=\u2009.01), and at 24\u2009months (p\u2009=\u2009.01) after CI activation. No significant associations in the subgroup implanted before 1\u2009year of life were observed. No significant associations between the BDNF rs6265 and LEAQ score were found. Multiple regression analysis (R2\u2009=\u2009.73) in the subgroup implanted after 1\u2009year of life revealed that MMP9 rs3918242 was a significant predictor of treatment outcome. In conclusion, C/C rs3918242 MMP9 predisposes their deaf carriers to better CI outcomes, especially when implanted after the first birthday, than carriers of C/T rs3918242MMP9.