Hangzhou Center for Disease Control and Prevention, Hangzhou, 310021, Zhejiang, China.
Department of Epidemiology and Biostatistics, Department of Respiratory, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Zhejiang, Hangzhou, 310058, People's Republic of China.
Environ Health. 2019 Apr 4;18(1):30. doi: 10.1186/s12940-019-0471-9.
The aim of this study was to screen for noise-induced hearing loss (NIHL)-associated single nucleotide polymorphisms (SNPs) and to construct genetic risk prediction models for NIHL in a Chinese population.
Four hundred seventy-six subjects with NIHL and 476 matched controls were recruited from a cross-sectional survey on NIHL in China. A total of 83 candidate SNPs were genotyped using nanofluidic dynamic arrays on a Fluidigm platform. NIHL-associated SNPs were screened with a multiple logistic model, and a genetic risk model was constructed based on the genetic risk score (GRS). The results were validated using a prospective cohort population.
Seven SNPs in the CDH23, PCDH15, EYA4, MYO1A, KCNMA1, and OTOG genes were significantly (P < 0.05) associated with the risk of NIHL, whereas seven other SNPs were marginally (P > 0.05 and P < 0.1) associated with the risk of NIHL. A positive correlation was observed between GRS values and odds ratio (OR) for NIHL. Two SNPs, namely, rs212769 and rs7910544, were validated in the cohort study. Subjects with higher GRS (≧9) showed a higher risk of NIHL incidence with an OR of 2.00 (95% CI = 1.04, 3.86).
Genetic susceptibility plays an important role in the incidence of NIHL. GRS values, which are based on NIHL-associated SNPs. GRS may be utilized in the evaluation of genetic risk for NIHL and in the determination of NIHL susceptibility.
本研究旨在筛选与噪声性听力损失（NIHL）相关的单核苷酸多态性（SNP），并构建中国人群中 NIHL 的遗传风险预测模型。
从中国一项关于 NIHL 的横断面研究中招募了 476 例 NIHL 患者和 476 名匹配对照。使用 Fluidigm 平台上的纳米流体动力学动态阵列对 83 个候选 SNP 进行基因分型。使用多因素逻辑回归模型筛选与 NIHL 相关的 SNP，并基于遗传风险评分（GRS）构建遗传风险模型。使用前瞻性队列人群验证结果。
CDH23、PCDH15、EYA4、MYO1A、KCNMA1 和 OTOG 基因中的 7 个 SNP 与 NIHL 风险显著相关（P<0.05），而另外 7 个 SNP 与 NIHL 风险呈边缘相关（P>0.05 和 P<0.1）。GRS 值与 NIHL 的比值比（OR）呈正相关。rs212769 和 rs7910544 这两个 SNP 在队列研究中得到了验证。GRS（≧9）较高的受试者发生 NIHL 的风险更高，OR 为 2.00（95%CI=1.04, 3.86）。
遗传易感性在 NIHL 的发病中起重要作用。基于与 NIHL 相关的 SNP 的 GRS 值可用于评估 NIHL 的遗传风险，并确定 NIHL 的易感性。
