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Toxicol Lett. 2014 Sep 2;229(2):327-32. doi: 10.1016/j.toxlet.2014.06.034. Epub 2014 Jun 25.

Genetic variants in SMARC genes are associated with DNA damage levels in Chinese population.

Author information

1
Department of Epidemiology and Biostatistics and Ministry of Education (MOE) Key Lab for Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.
2
Ministry of Education Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
3
Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.
4
Department of Epidemiology and Biostatistics and Ministry of Education (MOE) Key Lab for Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China; Section of Clinical Epidemiology, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing, Jiangsu, China; State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, China.
5
Department of Epidemiology and Biostatistics and Ministry of Education (MOE) Key Lab for Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China; Section of Clinical Epidemiology, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing, Jiangsu, China; State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, China. Electronic address: hbshen@njmu.edu.cn.

Abstract

The switching defective/sucrose nonfermenting (SWI/SNF) related, matrix associated, actin dependent regulators of chromatin (SMARC) are components of human SWI/SNF like chromatin remodeling protein complexes, which are essential in the process of DNA damage repair. In this study, we hypothesized that genetic variants in SMARC genes may modify the capacity of DNA repair to damage. To test this hypothesis, we genotyped a total of 20 polymorphisms in five key SMARC genes (SMARCA5, SMARCC2, SMARCD1, SMARCD2, SMARCD3) to evaluate their associations with DNA damage levels in 307 subjects. The DNA damage levels were measured with comet assay. The multiple linear regression was used to assess the relationship between each polymorphism and DNA damage levels in additive model. We found that the genotypes of rs6857360 (β=0.23, 95% CI=0.06-0.40, P=0.008) in SMARCA5, rs6919 (β=0.20, 95% CI=0.05-0.34, P=0.008) and rs2727280 (β=0.18, 95% CI=0.04-0.33, P=0.013) in SMARCD2, and rs17173769 (β=-0.27, 95% CI=-0.52 to -0.01, P=0.045) in SMARCD3 were significantly associated with DNA damage levels. After combining these four polymorphisms, we found that the more unfavorable alleles the subjects carried, the heavier DNA damage they suffered, suggesting a locus-dosage effect between combined genotypes and DNA damage levels (P for trend=0.006). These findings suggest that genetic variants in SMARC genes may contribute the individual variations of DNA damage levels in Chinese population. Further larger and functional studies are warranted to confirm our findings.

KEYWORDS:

Comet assay; DNA damage; Genetic variants; PM2.5 exposure; Population-based study; SMARC genes

PMID:
24973491
DOI:
10.1016/j.toxlet.2014.06.034
[Indexed for MEDLINE]

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