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基因变异与居住环境靠近农药喷洒区域对尿道下裂风险的联合影响。

Joint effects of genetic variants and residential proximity to pesticide applications on hypospadias risk.

作者信息

Carmichael Suzan L, Yang Wei, Ma Chen, Roberts Eric, Kegley Susan, English Paul, Lammer Edward J, Witte John S, Shaw Gary M

机构信息

Department of Pediatrics, Division of Neonatology and Developmental Medicine, Stanford University School of Medicine, Stanford, California.

Public Health Institute, Oakland, California.

出版信息

Birth Defects Res A Clin Mol Teratol. 2016 Aug;106(8):653-8. doi: 10.1002/bdra.23508. Epub 2016 Apr 21.

DOI:10.1002/bdra.23508
PMID:27098078
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4983249/
Abstract

BACKGROUND

We examined risks associated with joint exposure of gene variants and pesticides.

METHODS

Analyses included 189 cases and 390 male controls born from 1991 to 2003 in California's San Joaquin Valley. We used logistic regression to examine risks associated with joint exposures of gene variants and pesticides that our previous work identified as associated with hypospadias. Genetic variables were based on variants in DGKK, genes involved in sex steroid synthesis/metabolism, and genes involved in genital tubercle development. Pesticide exposure was based on residential proximity to commercial agricultural pesticide applications.

RESULTS

Odds ratios (ORs) were highest among babies with joint exposures, who had two- to fourfold increased risks; for example, the OR was 3.7 (95% confidence interval [CI], 0.8-16.5) among subjects with the risk-associated DGKK haplotype and pesticide exposure; OR, 1.5 (95% CI, 0.7-3.1) among subjects with the haplotype and no pesticide exposure; and OR, 0.9 (95% CI, 0.5-1.6) among subjects without the haplotype but with pesticide exposure, relative to subjects with neither. However, results did not provide statistical evidence that these risks were significantly greater than expected on an additive scale, relative to risks associated with one exposure at a time.

CONCLUSION

We observed elevated risks associated with joint exposures to selected pesticides and genetic variants but no statistical evidence for interaction. Birth Defects Research (Part A) 106:653-658, 2016. © 2016 Wiley Periodicals, Inc.

摘要

背景

我们研究了基因变异与农药联合暴露相关的风险。

方法

分析纳入了1991年至2003年在加利福尼亚州圣华金谷出生的189例病例和390名男性对照。我们使用逻辑回归来研究基因变异与农药联合暴露相关的风险,我们之前的研究已确定这些基因变异和农药与尿道下裂有关。基因变量基于DGKK中的变异、参与性类固醇合成/代谢的基因以及参与生殖结节发育的基因。农药暴露基于居住地与商业农业农药施用地点的距离。

结果

联合暴露的婴儿的优势比(OR)最高,其风险增加了两到四倍;例如,具有与风险相关的DGKK单倍型且接触农药的受试者的OR为3.7(95%置信区间[CI],0.8 - 16.5);具有该单倍型但未接触农药的受试者的OR为1.5(95%CI,0.7 - 3.1);相对于既无该单倍型也未接触农药的受试者,没有该单倍型但接触农药的受试者的OR为0.9(95%CI,0.5 - 1.6)。然而,结果并未提供统计学证据表明这些风险在相加尺度上显著大于预期,相对于一次仅一种暴露相关的风险。

结论

我们观察到与选定农药和基因变异的联合暴露相关的风险升高,但没有交互作用的统计学证据。《出生缺陷研究(A部分)》106:653 - 658,2016年。©2016威利期刊公司。

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本文引用的文献

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Environmental, parental and gestational factors that influence the occurrence of hypospadias in male patients.影响男性患者尿道下裂发生的环境、父母及孕期因素。
J Pediatr Urol. 2015 Feb;11(1):12-9. doi: 10.1016/j.jpurol.2014.10.003. Epub 2015 Feb 3.
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Genetic and environmental origins of hypospadias.尿道下裂的遗传和环境起源
Curr Opin Endocrinol Diabetes Obes. 2014 Jun;21(3):227-32. doi: 10.1097/MED.0000000000000063.
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Hypospadias and variants in genes related to sex hormone biosynthesis and metabolism.与性激素生物合成和代谢相关基因的尿道下裂和变异。
Andrology. 2014 Jan;2(1):130-7. doi: 10.1111/j.2047-2927.2013.00165.x. Epub 2013 Nov 26.
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