Dawes Piers, Platt Hazel, Horan Michael, Ollier William, Munro Kevin, Pendleton Neil, Payton Antony
School of Psychological Sciences, Salford Royal NHS Hospital, Manchester, United Kingdom.
Laryngoscope. 2015 Jan;125(1):E33-8. doi: 10.1002/lary.24898. Epub 2014 Aug 22.
OBJECTIVES/HYPOTHESIS: Age-related hearing loss has a genetic component, but there have been limited genetic studies in this field. Both N-acetyltransferase 2 and apolipoprotein E genes have previously been associated. However, these studies have either used small sample sizes, examined a limited number of polymorphisms, or have produced conflicting results. Here we use a haplotype tagging approach to determine association with age-related hearing loss and investigate epistasis between these two genes.
Candidate gene association study of a continuous phenotype.
We investigated haplotype tagging single nucleotide polymorphisms in the N-acetyltransferase 2 gene and the presence/absence of the apolipoprotein E ε4 allele for association with age-related hearing loss in a cohort of 265 Caucasian elderly volunteers from Greater Manchester, United Kingdom. Hearing phenotypes were generated using principal component analysis of the hearing threshold levels for the better ear (severity, slope, and concavity). Genotype data for the N-acetyltransferase 2 gene was obtained from existing genome-wide association study data from the Illumina 610-Quadv1 chip. Apolipoprotein E genotyping was performed using Sequenom technology. Linear regression analysis was performed using Plink and Stata software.
No significant associations (P value, > 0.05) were observed between the N-acetyltransferase 2 or apolipoprotein E gene polymorphisms and any hearing factor. No significant association was observed for epistasis analysis of apolipoprotein E ε4 and the N-acetyltransferase 2 single nucleotide polymorphism rs1799930 (NAT2*6A).
We found no evidence to support that either N-acetyltransferase 2 or apolipoprotein E gene polymorphisms are associated with age-related hearing loss in a cohort of 265 elderly volunteers.
目的/假设：年龄相关性听力损失具有遗传因素，但该领域的遗传学研究有限。此前已发现N-乙酰基转移酶2和载脂蛋白E基因都与之相关。然而，这些研究要么样本量小，要么检测的多态性数量有限，要么结果相互矛盾。在此，我们采用单倍型标签法来确定与年龄相关性听力损失的关联，并研究这两个基因之间的上位性。
对连续表型进行候选基因关联研究。
我们在来自英国大曼彻斯特的265名白种人老年志愿者队列中，研究了N-乙酰基转移酶2基因中的单倍型标签单核苷酸多态性以及载脂蛋白E ε4等位基因的有无与年龄相关性听力损失的关联。听力表型通过对较好耳听力阈值水平进行主成分分析得出（严重程度、斜率和凹度）。N-乙酰基转移酶2基因的基因型数据来自Illumina 610 - Quadv1芯片的现有全基因组关联研究数据。载脂蛋白E基因分型采用Sequenom技术。使用Plink和Stata软件进行线性回归分析。
未观察到N-乙酰基转移酶2或载脂蛋白E基因多态性与任何听力因素之间存在显著关联（P值>0.05）。对于载脂蛋白E ε4与N-乙酰基转移酶2单核苷酸多态性rs1799930（NAT2*6A）的上位性分析，也未观察到显著关联。
在265名老年志愿者队列中，我们没有发现证据支持N-乙酰基转移酶2或载脂蛋白E基因多态性与年龄相关性听力损失有关。
