Konings Annelies, Van Laer Lut, Michel Sophie, Pawelczyk Malgorzata, Carlsson Per-Inge, Bondeson Marie-Louise, Rajkowska Elzbieta, Dudarewicz Adam, Vandevelde Ann, Fransen Erik, Huyghe Jeroen, Borg Erik, Sliwinska-Kowalska Mariola, Van Camp Guy
Department of Medical Genetics, University of Antwerp, Antwerp, Belgium.
Eur J Hum Genet. 2009 Mar;17(3):329-35. doi: 10.1038/ejhg.2008.172. Epub 2008 Sep 24.
Noise-induced hearing loss (NIHL) is one of the most important occupational health hazards. Millions of people worldwide are exposed daily to harmful levels of noise. NIHL is a complex disease resulting from an interaction between genetic and environmental factors. Although the environmental risk factors have been studied extensively, little is known about the genetic factors. Heat-shock proteins (HSPs) are induced after exposure to severe noise. When first induced by exposure to moderate sound levels, they can protect the ear from damage from excessive noise exposure. This protection is highly variable between individuals. An association of HSP70 genes with NIHL has been described by Yang et al (2006) in a Chinese sample set of noise-exposed workers. In this study, three polymorphisms (rs1043618, rs1061581 and rs2227956) in HSP70-1, HSP70-2 and HSP70-hom, respectively, were genotyped in 206 Swedish and 238 Polish DNA samples of noise-exposed subjects and analyzed. One SNP, rs2227956 in HSP70-hom, resulted in a significant association with NIHL in both sample sets. In addition, rs1043618 and rs1061581 were significant in the Swedish sample set. Analysis of the haplotypes composed of the three SNPs revealed significant associations between NIHL and haplotype GAC in both sample sets and with haplotype CGT in the Swedish sample set. In conclusion, this study replicated the association of HSP70 genes with NIHL in a second and third independent noise-exposed sample set, hereby adding to the evidence that HSP70 genes may be NIHL susceptibility genes.
噪声性听力损失(NIHL)是最重要的职业健康危害之一。全球数百万人每天都暴露在有害水平的噪声中。NIHL是一种由遗传和环境因素相互作用导致的复杂疾病。尽管对环境风险因素进行了广泛研究,但对遗传因素却知之甚少。热休克蛋白(HSPs)在暴露于高强度噪声后被诱导产生。当首次由中等强度声音暴露诱导产生时,它们可以保护耳朵免受过度噪声暴露的损害。这种保护在个体之间差异很大。Yang等人(2006年)在中国一组噪声暴露工人的样本中描述了HSP70基因与NIHL的关联。在本研究中,分别对206名瑞典和238名波兰噪声暴露受试者的DNA样本中的HSP70-1、HSP70-2和HSP70-hom中的三个多态性(rs1043618、rs1061581和rs2227956)进行基因分型并分析。其中一个单核苷酸多态性,即HSP70-hom中的rs2227956,在两个样本组中均与NIHL存在显著关联。此外,rs1043618和rs1061581在瑞典样本组中具有显著性。对由这三个单核苷酸多态性组成的单倍型进行分析发现,在两个样本组中NIHL与单倍型GAC之间存在显著关联,在瑞典样本组中与单倍型CGT存在显著关联。总之,本研究在第二个和第三个独立的噪声暴露样本组中重复了HSP70基因与NIHL的关联,从而进一步证明HSP70基因可能是NIHL易感基因。