Breton Carrie V, Vora Hita, Salam Muhammad T, Islam Talat, Wenten Made, Gauderman W James, Van den Berg David, Berhane Kiros, Peters John M, Gilliland Frank D
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, 90033 USA.
Am J Respir Crit Care Med. 2009 Apr 1;179(7):601-7. doi: 10.1164/rccm.200809-1384OC. Epub 2009 Jan 16.
The glutathione S-transferases (GSTs) are important detoxification enzymes.
To investigate effects of variants in GST mu genes on lung function and assess their interactions with tobacco smoke exposure.
In this prospective study, 14,836 lung function measurements were collected from 2,108 children who participated in two Southern California cohorts. For each child, tagging single nucleotide polymorphisms in GSTM2, GSTM3, GSTM4, and GSTM5 loci were genotyped. Using principal components and haplotype analyses, the significance of each locus in relation to level and growth of FEV1, maximum midexpiratory flow rate (MMEF), and FVC was evaluated. Interactions between loci and tobacco smoke on lung function were also investigated.
Variation in the GST mu family locus was associated with lower FEV1 (P = 0.01) and MMEF (0.04). Two haplotypes of GSTM2 were associated with FEV1 and MMEF, with effect estimates in opposite directions. One haplotype in GSTM3 showed a decrease in growth for MMEF (-164.9 ml/s) compared with individuals with other haplotypes. One haplotype in GSTM4 showed significantly decreased growth in FEV1 (-51.3 ml), MMEF (-69.1 ml/s), and FVC (-44.4 ml), compared with all other haplotypes. These results were consistent across two independent cohorts. Variation in GSTM2 was particularly important for FVC and FEV(1) among children whose mothers smoked during pregnancy.
Genetic variation across the GST mu locus is associated with 8-year lung function growth. Children of mothers who smoked during pregnancy and had variation in GSTM2 had lower lung function growth.
谷胱甘肽S-转移酶（GSTs）是重要的解毒酶。
研究GSTμ基因变异对肺功能的影响，并评估其与烟草烟雾暴露的相互作用。
在这项前瞻性研究中，从参与南加州两个队列研究的2108名儿童中收集了14836次肺功能测量数据。对每个儿童的GSTM2、GSTM3、GSTM4和GSTM5基因座中的标签单核苷酸多态性进行基因分型。使用主成分分析和单倍型分析，评估每个基因座与第一秒用力呼气容积（FEV1）、最大呼气中期流速（MMEF）和用力肺活量（FVC）水平及增长的相关性。还研究了基因座与烟草烟雾对肺功能的相互作用。
GSTμ家族基因座的变异与较低的FEV1（P = 0.01）和MMEF（P = 0.04）相关。GSTM2的两种单倍型与FEV1和MMEF相关，效应估计方向相反。与其他单倍型个体相比，GSTM3中的一种单倍型显示MMEF增长下降（-164.9 ml/s）。与所有其他单倍型相比，GSTM4中的一种单倍型显示FEV1（-51.3 ml）、MMEF（-69.1 ml/s）和FVC（-44.4 ml）的增长显著下降。这些结果在两个独立队列中是一致的。在母亲孕期吸烟孩子中，GSTM2的变异对FVC和FEV1尤为重要。
GSTμ基因座的遗传变异与8年肺功能增长相关。母亲孕期吸烟且GSTM2有变异的儿童肺功能增长较低。
