Wenten Madé, Li Yu-Fen, Lin Pi-Chu, Gauderman W James, Berhane Kiros, Avol Edward, Gilliland Frank D
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA.
Pediatrics. 2009 May;123(5):1344-51. doi: 10.1542/peds.2008-1892.
The GSTP1 Ile105Val variant and secondhand tobacco smoke exposure have been independently associated with acute respiratory illness; however, susceptibility to in utero and secondhand tobacco smoke has yet to be examined in relation to variation across the GSTP1 locus.
The purpose of this work was to determine whether variation across the GSTP1 locus is associated with respiratory illness-related school absences and to determine whether this relationship varies by in utero and secondhand tobacco smoke exposure.
Tobacco smoke exposure status, incident respiratory-related school absence records, and DNA samples was ascertained for 1132 Hispanic and non-Hispanic white elementary school children as part of the Children's Health Study.
Four GSTP1 single-nucleotide polymorphisms were selected that accounted for 93% of the variation across the locus. Individual single-nucleotide polymorphism analyses showed a protective effect for the minor alleles in single-nucleotide polymorphisms 1 (rs6591255), 3 (GSTP1 Ile105Val: rs1695), and 4 (rs749174) for respiratory illness. The haplotype, which includes a minor allele for single-nucleotide polymorphisms 1, 3, and 4 (h1011), was associated with a decreased risk of respiratory illness. The protective effect of GSTP1 variants was lost among individuals exposed to in utero and secondhand tobacco smoke.
A common GSTP1 haplotype, which includes the functional Ile105Val polymorphism, was associated with respiratory-related school absences. The protection afforded by this haplotype was lost in children exposed to involuntary tobacco smoke. The paradigm of loss of genetic protection among those exposed to tobacco smoke has clinical and public health implications that warrant broader consideration in research and practice.
谷胱甘肽S-转移酶P1（GSTP1）基因第105位密码子异亮氨酸（Ile）突变为缬氨酸（Val）的变异以及二手烟暴露均与急性呼吸道疾病独立相关；然而，GSTP1基因座变异与宫内及二手烟易感性之间的关系尚待研究。
本研究旨在确定GSTP1基因座变异是否与呼吸系统疾病相关的缺课情况有关，并确定这种关系是否因宫内及二手烟暴露而有所不同。
作为儿童健康研究的一部分，对1132名西班牙裔和非西班牙裔白人小学生确定了烟草烟雾暴露状况、呼吸系统疾病相关的缺课记录以及DNA样本。
选择了4个GSTP1单核苷酸多态性，它们占该基因座变异的93%。单个单核苷酸多态性分析显示，单核苷酸多态性1（rs6591255）、3（GSTP1 Ile105Val：rs1695）和4（rs749174）中的次要等位基因对呼吸系统疾病具有保护作用。包含单核苷酸多态性1、3和4次要等位基因的单倍型（h1011）与呼吸系统疾病风险降低相关。GSTP1变异的保护作用在暴露于宫内及二手烟的个体中消失。
一种常见的GSTP1单倍型，包括功能性的Ile105Val多态性，与呼吸系统疾病相关的缺课情况有关。这种单倍型提供的保护作用在暴露于非自愿吸烟的儿童中消失。烟草烟雾暴露者遗传保护丧失的模式具有临床和公共卫生意义，值得在研究和实践中进行更广泛的考虑。
