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N-乙酰转移酶2基因多态性NAT2*6A对年龄相关性听力减退的影响

Contribution of the N-acetyltransferase 2 polymorphism NAT2*6A to age-related hearing impairment.

作者信息

Van Eyken E, Van Camp G, Fransen E, Topsakal V, Hendrickx J J, Demeester K, Van de Heyning P, Mäki-Torkko E, Hannula S, Sorri M, Jensen M, Parving A, Bille M, Baur M, Pfister M, Bonaconsa A, Mazzoli M, Orzan E, Espeso A, Stephens D, Verbruggen K, Huyghe J, Dhooge I, Huygen P, Kremer H, Cremers C W R J, Kunst S, Manninen M, Pyykkö I, Lacava A, Steffens M, Wienker T F, Van Laer L

机构信息

Department of Medical Genetics, University of Antwerp, Antwerp, Belgium.

出版信息

J Med Genet. 2007 Sep;44(9):570-8. doi: 10.1136/jmg.2007.049205. Epub 2007 May 18.

Abstract

BACKGROUND

Age-related hearing impairment (ARHI) is the most common sensory impairment in older people, affecting 50% of those aged 80 years. The proportion of older people is increasing in the general population, and as a consequence, the number of people affected with ARHI is growing. ARHI is a complex disorder, with both environmental and genetic factors contributing to the disease. The first studies to elucidate these genetic factors were recently performed, resulting in the identification of the first two susceptibility genes for ARHI, NAT2 and KCNQ4.

METHODS

In the present study, the association between ARHI and polymorphisms in genes that contribute to the defence against reactive oxygen species, including GSTT1, GSTM1 and NAT2, was tested. Samples originated from seven different countries and were combined into two test population samples, the general European population and the Finnish population. Two distinct phenotypes for ARHI were studied, Z(low) and Z(high), representing hearing in the low and high frequencies, respectively. Statistical analysis was performed for single polymorphisms (GSTM1, GSTT1, NAT25A, NAT26A, and NAT2*7A), haplotypes, and gene-environment and gene-gene interactions.

RESULTS

We found an association between ARHI and GSTT1 and GSTM1 in the Finnish population sample, and with NAT2*6A in the general European population sample. The latter finding replicates previously published data.

CONCLUSION

As replication is considered the ultimate proof of true associations in the study of complex disorders, this study provides further support for the involvement of NAT2*6A in ARHI.

摘要

背景

年龄相关性听力减退(ARHI)是老年人中最常见的感觉障碍,影响着50%的80岁老人。老年人口在总人口中的比例正在增加,因此,受ARHI影响的人数也在增长。ARHI是一种复杂的疾病,环境和遗传因素均对该病有影响。最近开展了首批阐明这些遗传因素的研究,从而确定了ARHI的前两个易感基因,即NAT2和KCNQ4。

方法

在本研究中,对ARHI与有助于抵御活性氧的基因多态性之间的关联进行了检测,这些基因包括GSTT1、GSTM1和NAT2。样本来自七个不同国家,并合并为两个测试人群样本,即欧洲普通人群样本和芬兰人群样本。对ARHI的两种不同表型Z(低)和Z(高)进行了研究,分别代表低频和高频听力。针对单核苷酸多态性(GSTM1、GSTT1、NAT25A、NAT26A和NAT2*7A)、单倍型以及基因-环境和基因-基因相互作用进行了统计分析。

结果

我们在芬兰人群样本中发现ARHI与GSTT1和GSTM1之间存在关联,在欧洲普通人群样本中发现ARHI与NAT2*6A存在关联。后一发现重复了先前发表的数据。

结论

由于在复杂疾病研究中,重复被认为是真正关联的最终证据,因此本研究为NAT2*6A参与ARHI提供了进一步支持。

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