CASP9 genotype confers gentamicin susceptibility in intratympanic treatment of intractable vertigo caused by Ménière’s disease

Abstract

Background: Ménière’s disease (MD) is a disorder of the inner ear, causing episodes of vertigo. Although surgery is reserved for intractable MD, intratympanic gentamicin (ITG) injection has become an alternative for controlling vertigo.

Aims/Objectives: To investigate the genetic basis of ITG efficacy.

Material and methods: We hypothesized that single nucleotide polymorphisms (SNPs) affect outcomes in patients with MD who receive ITG injections. Whole-exome sequencing was used to determine variations in coding regions.

Results: Multivariate analysis revealed two SNPs, rs1052571 in caspase 9 (CASP9; p = .017) and rs3745274 in cytochrome P450 2B6 (p = .053), which were associated with susceptibility to ITG injections. Only the C-allele in the rs1052571 SNP was significantly associated with susceptibility (p = .027; odds ratio: 5.95; 95% confidence interval: 1.26–28.57, by Fisher’s exact test).

Conclusions and significance: Our results elucidated the role of the rs1052571 SNP and provide a genetic perspective on gentamicin efficacy (susceptibility) in treating intractable MD.

Chinese abstract

背景：Ménière病（MD）是一种内耳疾病, 会引起眩晕发作。对于难治的MD, 必须依靠手术治疗。尽管如此, 鼓膜内注射庆大霉素（ITG）已成为控制眩晕的另一种方法。

目的：探讨ITG疗效的遗传基础。

材料和方法：我们假设单核苷酸多态性（SNPs）影响接受ITG注射的MD患者的治疗结果。全外显子测序用于确定编码区的变异性。

结果：多变量分析显示两个单核苷酸多态性, 分别为半胱天冬酶 9（CASP9； p = .017）和细胞色素P450 2B6（p=.053）中的rs1052571和rs375274。它们与ITG注射的易感性相关。只有rs1052571单核苷酸多态性中的c等位基因与易感性显著相关（根据Fisher的精确检验, p=.027；优势比：5.95；95%置信区间：1.26–28.57）。

结论与意义：我们的研究结果阐明了rs1052571单核苷酸多态性的作用, 并为庆大霉素治疗难治性MD的疗效（易感性）提供了遗传学基础。

Keywords:

• Ménière’s disease
• intratympanic gentamicin treatment
• single nucleotide polymorphism
• caspase 9
• cytochrome P450 2B6

Acknowledgments

The authors thank all the participants who made this study possible. This manuscript was edited by Wallace Academic Editing.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This research was supported by the grant provided by Cathay General Hospital [MR-10303].