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Abstract：
BACKGROUND: Previous studies have implicated inherited mutations in mitochondrial DNA (mtDNA) in sensorineural hearing loss (SNHL). However, the definitive association between mitochondrial 12S rRNA (MT-RNR1) variants and hearing loss in the population has not been well established, particularly in Asia. The objective of this retrospective cohort study was to assess the association between MT-RNR1 variants and the risk of SNHL in patients in Taiwan.
METHODS: The cohort included 306,068 participants from Taiwan between January 2003 and December 2020. Participants were classified based on genetic variants, particularly mitochondrial mutations (rs267606618, rs267606619, rs267606617). MT-RNR1 variant cases were matched 1:10 with non-mutant patients by age, gender, and visit year, excluding those with pre-existing hearing loss. The primary endpoint was SNHL, identified using specific ICD-TM codes with a 90% positive predictive value. Medication exposure history was determined via self-report or electronic medical records in the hospital. Cox proportional hazard regression models were used to assess the association between MT-RNR1 variants and hearing loss, adjusting for various covariates. Kaplan-Meier survival curves and log-rank tests compared hearing loss incidence between groups.
RESULTS: The mean age of the mtDNA variants group is 32.4 years, with a standard deviation of 19.2 years. The incidence density of hearing loss for the mutation group was 36.42 per 10,000 person-years (95% Confidence Interval [CI], 27.21-47.73), which was higher than the 23.77per 10,000 person-years (95% CI, 21.32-26.42) in the wild-type group (p = 0.0036). Additionally, diabetes mellitus was associated with an increased risk of developing SNHL in individuals with MT-RNR1 variants (adjusted hazard ratio = 1.76 [95% CI, 1.00-3.09], p < 0.05).
CONCLUSIONS: This study highlights the increased risk of hearing loss in patients carrying MT-RNR1 variants, particularly those with diabetes mellitus. Future research that integrates genetic and clinical data is crucial for developing more precise interventions to monitor and treat hearing loss in this vulnerable population.
METHODS: The cohort included 306,068 participants from Taiwan between January 2003 and December 2020. Participants were classified based on genetic variants, particularly mitochondrial mutations (rs267606618, rs267606619, rs267606617). MT-RNR1 variant cases were matched 1:10 with non-mutant patients by age, gender, and visit year, excluding those with pre-existing hearing loss. The primary endpoint was SNHL, identified using specific ICD-TM codes with a 90% positive predictive value. Medication exposure history was determined via self-report or electronic medical records in the hospital. Cox proportional hazard regression models were used to assess the association between MT-RNR1 variants and hearing loss, adjusting for various covariates. Kaplan-Meier survival curves and log-rank tests compared hearing loss incidence between groups.
RESULTS: The mean age of the mtDNA variants group is 32.4 years, with a standard deviation of 19.2 years. The incidence density of hearing loss for the mutation group was 36.42 per 10,000 person-years (95% Confidence Interval [CI], 27.21-47.73), which was higher than the 23.77per 10,000 person-years (95% CI, 21.32-26.42) in the wild-type group (p = 0.0036). Additionally, diabetes mellitus was associated with an increased risk of developing SNHL in individuals with MT-RNR1 variants (adjusted hazard ratio = 1.76 [95% CI, 1.00-3.09], p < 0.05).
CONCLUSIONS: This study highlights the increased risk of hearing loss in patients carrying MT-RNR1 variants, particularly those with diabetes mellitus. Future research that integrates genetic and clinical data is crucial for developing more precise interventions to monitor and treat hearing loss in this vulnerable population.
摘要：
背景：先前的研究表明，线粒体DNA（mtDNA）的遗传突变与感觉神经性听力损失（SNHL）有关。然而,线粒体12SrRNA（MT-RNR1）变异与人群听力损失之间的明确关联尚未得到很好的确定，特别是在亚洲。这项回顾性队列研究的目的是评估台湾患者MT-RNR1变异与SNHL风险之间的关系。
方法：该队列包括2003年1月至2020年12月来自台湾的306,068名参与者。参与者根据遗传变异进行分类，特别是线粒体突变（rs267606618，rs267606619，rs267606617）。MT-RNR1变异病例与非突变患者按年龄1:10匹配，性别,访问年，不包括那些预先存在听力损失的人。主要终点是SNHL,使用特定的ICD-TM代码识别，阳性预测值为90%。通过医院的自我报告或电子病历确定药物暴露史。Cox比例风险回归模型用于评估MT-RNR1变异与听力损失之间的关联。调整各种协变量。Kaplan-Meier存活曲线和log-rank检验比较了组间听力损失发生率。
结果：mtDNA变异组的平均年龄为32.4岁，标准差为19.2年。突变组的听力损失发生率为36.42/10,000人年（95％置信区间[CI]，27.21-47.73),高于野生型组的23.77/10,000人年（95％CI，21.32-26.42）（p=0.0036）。此外,糖尿病与MT-RNR1变异个体发生SNHL的风险增加相关(调整后的风险比=1.76[95%CI,1.00-3.09],p<0.05)。
结论：这项研究强调了携带MT-RNR1变体的患者听力损失的风险增加，尤其是糖尿病患者。整合遗传和临床数据的未来研究对于开发更精确的干预措施来监测和治疗这一弱势群体的听力损失至关重要。
方法：该队列包括2003年1月至2020年12月来自台湾的306,068名参与者。参与者根据遗传变异进行分类，特别是线粒体突变（rs267606618，rs267606619，rs267606617）。MT-RNR1变异病例与非突变患者按年龄1:10匹配，性别,访问年，不包括那些预先存在听力损失的人。主要终点是SNHL,使用特定的ICD-TM代码识别，阳性预测值为90%。通过医院的自我报告或电子病历确定药物暴露史。Cox比例风险回归模型用于评估MT-RNR1变异与听力损失之间的关联。调整各种协变量。Kaplan-Meier存活曲线和log-rank检验比较了组间听力损失发生率。
结果：mtDNA变异组的平均年龄为32.4岁，标准差为19.2年。突变组的听力损失发生率为36.42/10,000人年（95％置信区间[CI]，27.21-47.73),高于野生型组的23.77/10,000人年（95％CI，21.32-26.42）（p=0.0036）。此外,糖尿病与MT-RNR1变异个体发生SNHL的风险增加相关(调整后的风险比=1.76[95%CI,1.00-3.09],p<0.05)。
结论：这项研究强调了携带MT-RNR1变体的患者听力损失的风险增加，尤其是糖尿病患者。整合遗传和临床数据的未来研究对于开发更精确的干预措施来监测和治疗这一弱势群体的听力损失至关重要。
