Effect of glutathione S-transferase polymorphisms and proximity to hazardous waste sites on time to systemic lupus erythematosus diagnosis - Results from the Roxbury Lupus Project
Effect of glutathione S-transferase polymorphisms and proximity to hazardous waste sites on time to systemic lupus erythematosus diagnosis - Results from the Roxbury Lupus Project
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DOI：
10.1002/art.22308
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发表时间：
2007-01-01
影响因子：
--
通讯作者：
Fraser, Patricia A.
中科院分区：
文献类型：
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作者：
Karlson, Elizabeth W.;Watts, Julie;Fraser, Patricia A.
Objective.非裔美国女性系统性红斑狼疮（SLE）的高患病率可能是由于环境暴露、遗传因素或多种因素的组合。我们的目标是评估与危险废物场所的住宅接近程度和3种谷胱甘肽S-转移酶（GST）基因（GSTM 1、GSTT 1和GSTP 1）的遗传变异与诊断SLE时的年龄之间的关联。居住历史是通过采访93例SLE患者从3个主要是非洲裔美国人在波士顿的社区。使用ArcView软件对研究区域内416个危险废物场址的居住地址和位置进行了地理编码。采用时变考克斯模型研究居民与危险场所的接近程度、GST基因型以及基因型与暴露之间的交互作用对诊断年龄的影响。这些社区的非裔美国妇女SLE患病率为3.56例/1000。GSTM 1-null和GSTP 1 Ile 105 Val的纯合性与SLE的早期诊断相关（P = 0.03），但与416个危险部位的邻近性无关。关于特定场地污染物的可验证数据表明，在67个场地的子集中，暴露于挥发性有机化合物的潜在风险较高（Bonferroni校正后P < 0.05）。在仅限于这些位点的分析中，GST基因型与邻近性有显著的交互作用（P = 0.03）。在这个城市人群中，危险废物场地的住宅邻近度与SLE早期诊断风险之间没有独立的相关性。然而，有限数量的网站的分析表明，早期SLE的风险与接近危险的网站可能是由GST多态性调制。
Objective. The high prevalence of systemic lupus erythematosus (SLE) among African American women may be due to environmental exposures, genetic factors, or a combination of factors. Our goal was to assess association of residential proximity to hazardous waste sites and genetic variation in 3 glutathione S- transferase (GST) genes (GSTM1, GSTT1, and GSTP1) with age at diagnosis of SLE.Methods. Residential histories were obtained by interviewing 93 SLE patients from 3 predominantly African American neighborhoods in Boston. Residential addresses and locations of 416 hazardous waste sites in the study area were geocoded using ArcView software. Time-varying Cox models were used to study the effect of residential proximity to hazardous sites, GST genotype, and interaction between genotype and exposure in determining age at diagnosis.Results. The prevalence of SLE among African American women in these neighborhoods was 3.56 SLE cases per 1,000. Homozygosity for GSTM1-null and GSTP1 Ile105Val in combination was associated with earlier SLE diagnosis (P = 0.03), but there was no association with proximity to 416 hazardous sites. Avail-able data on specific site contaminants suggested that, at a subset of 67 sites, there was higher potential risk for exposure to volatile organic compounds (P < 0.05 with Bonferroni correction). GST genotypes had a significant interaction with proximity (P = 0.03) in analyses limited to these sites.Conclusion. There was no independent association between residential proximity to hazardous waste sites and the risk of earlier SLE diagnosis in this urban population. However, analysis of a limited number of sites indicated that the risk of earlier SLE associated with proximity to hazardous sites might be modulated by GST polymorphisms.