Objective The effects of interactions between genetic and environmental factors on the noise-induced hearing loss(NIHL)are still unclear.This study aimed to assess interactions among gene polymorphisms,noise metrics,a...Objective The effects of interactions between genetic and environmental factors on the noise-induced hearing loss(NIHL)are still unclear.This study aimed to assess interactions among gene polymorphisms,noise metrics,and lifestyles on the risk of NIHL.Methods A case-control study was conducted using 307 patients with NIHL and 307 matched healthy individuals from five manufacturing industries.General demographic data,lifestyle details,and noise exposure levels were recorded.The Kompetitive allele-specific polymerase chain reaction(KASP)was used to analyze the genotypes of 18 SNPs.Results GMDR model demonstrated a relevant interaction between NRN1 rs3805789 and CAT rs7943316(P=0.0107).Subjects with T allele of rs3805789 or T allele of rs7943316 had higher risks of NIHL than those with the SNP pair of rs3805789-CC and rs7943316-AA(P<0.05).There was an interaction among rs3805789,rs7943316,and kurtosis(P=0.0010).Subjects exposed to complex noise and carrying both rs3805789-CT and rs7943316-TT or rs3805789-CT/TT and rs7943316-AA had higher risks of NIHL than those exposed to steady noise and carrying both rs3805789-CC and rs7943316-AA(P<0.05).The best six-locus model involving NRN1 rs3805789,CAT rs7943316,smoking,video volume,physical exercise,and working pressure for the risk of NIHL was found to be the interaction(P=0.0010).An interaction was also found among smoking,video volume,physical exercise,working pressure,and kurtosis(P=0.0107).Conclusion Concurrence of NRN1 and CAT constitutes a genetic risk factor for NIHL.Complex noise exposure significantly increases the risk of NIHL in subjects with a high genetic risk score.Interactions between genes and lifestyles as well as noise metrics and lifestyles affect the risk of NIHL.展开更多
文摘目的:非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)存在明显的遗传易感性,脂肪细胞因子通过参与胰岛素抵抗和肝脏脂肪变性等过程,在NAFLD的发生和发展中发挥重要作用,但参与脂肪细胞因子通路的基因与NAFLD之间的关联仍不明确。本研究旨在探索脂肪细胞因子通路的基因多态性位点及其交互作用与肥胖儿童NAFLD的关联。方法:采用病例对照研究,将肥胖儿童分为NAFLD组和对照组。采集受试者外周静脉血2 mL,提取DNA后采用多重PCR和高通量测序对脂肪细胞因子通路的14个单核苷酸多态性(single nucleotide polymorphism,SNP)进行分型检测。采用单因素及多因素Logistic回归分析各SNP与肥胖儿童NAFLD的关联。基于显性模型,联合使用交叉分析和Logistic回归分析相加或相乘交互作用。采用广义多因子降维法(generalized multifactor dimensionality reduction,GMDR)检测14个SNP之间基因-基因交互作用与肥胖儿童NAFLD之间的关联。结果:共纳入1 022例儿童,NAFLD组与对照组各511例。在调整年龄、性别、BMI后,多因素Logistic回归结果显示:PPARG rs1801282在3个遗传模型中与肥胖儿童NAFLD存在关联,分别是杂合子模型(CG vs CC,OR=0.58,95%CI 0.36~0.95,P=0.029)、显性模型(CG+GG vs CC,OR=0.62,95%CI 0.38~1.00,P=0.049)、超显性模型(CC+GG vs CG,OR=1.72,95%CI 1.06~2.80,P=0.028);PRKAG2 rs12703159在4个遗传模型中与肥胖儿童NAFLD存在关联,分别是杂合子模型(CT vs CC,OR=1.51,95%CI 1.10~2.07,P=0.011)、显性模型(CT+TT vs CC,OR=1.50,95%CI 1.10~2.03,P=0.010)、超显性模型(CC+TT vs CT,OR=0.67,95%CI 0.49~0.92,P=0.012)、加性模型(CC vs CT vs TT,OR=1.40,95%CI 1.07~1.83,P=0.015)。但PPARG rs1801282与PRKAG2 rs12703159间的相乘及相加交互作用均与肥胖儿童NAFLD不存在关联。经GMDR分析,调整年龄、性别、BMI后,14个SNP之间的交互作用均无统计学意义(均P>0.05)。结论:PPARG rs1801282、PRKAG2 rs12703159突变型与肥胖儿童NAFLD存在关联,但未发现SNP交互作用与肥胖儿童NAFLD之间的关联。
基金supported by Zhejiang Key Research and Development Program of China[No.2015C03039,No.20152013A01]Zhejiang Provincial Program for the Cultivation of High-level Innovative Health Talents,China+2 种基金Zhejiang Health Innovative Talent Training Project of Chinageneral scientific research project of Zhejiang Science and Technology Department of China[No.Y201941671]Natural Science Foundation of Zhejiang Provincial,China[LY18H260002]。
文摘Objective The effects of interactions between genetic and environmental factors on the noise-induced hearing loss(NIHL)are still unclear.This study aimed to assess interactions among gene polymorphisms,noise metrics,and lifestyles on the risk of NIHL.Methods A case-control study was conducted using 307 patients with NIHL and 307 matched healthy individuals from five manufacturing industries.General demographic data,lifestyle details,and noise exposure levels were recorded.The Kompetitive allele-specific polymerase chain reaction(KASP)was used to analyze the genotypes of 18 SNPs.Results GMDR model demonstrated a relevant interaction between NRN1 rs3805789 and CAT rs7943316(P=0.0107).Subjects with T allele of rs3805789 or T allele of rs7943316 had higher risks of NIHL than those with the SNP pair of rs3805789-CC and rs7943316-AA(P<0.05).There was an interaction among rs3805789,rs7943316,and kurtosis(P=0.0010).Subjects exposed to complex noise and carrying both rs3805789-CT and rs7943316-TT or rs3805789-CT/TT and rs7943316-AA had higher risks of NIHL than those exposed to steady noise and carrying both rs3805789-CC and rs7943316-AA(P<0.05).The best six-locus model involving NRN1 rs3805789,CAT rs7943316,smoking,video volume,physical exercise,and working pressure for the risk of NIHL was found to be the interaction(P=0.0010).An interaction was also found among smoking,video volume,physical exercise,working pressure,and kurtosis(P=0.0107).Conclusion Concurrence of NRN1 and CAT constitutes a genetic risk factor for NIHL.Complex noise exposure significantly increases the risk of NIHL in subjects with a high genetic risk score.Interactions between genes and lifestyles as well as noise metrics and lifestyles affect the risk of NIHL.
