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Genetic variants in multisynthetase complex genes are associated with DNA damage levels in Chinese populations.
- Source :
-
Mutation research [Mutat Res] 2016 Apr; Vol. 786, pp. 8-13. Date of Electronic Publication: 2016 Jan 25. - Publication Year :
- 2016
-
Abstract
- Aminoacyl-tRNA synthetases (ARSs) and ARS-interacting multi-functional proteins (AIMPs) form a multisynthetase complex (MSC) and play an important role in the process of DNA damage repair. We hypothesized that genetic variants in key ARSs and AIMPs might regulate the DNA damage response. Therefore, we systematically screened 23 potentially functional polymorphisms in MSC genes and evaluated the association between the genetic variants and DNA damage levels in 307 subjects from three cities in southern, central and northern China (Zhuhai, Wuhan and Tianjin, respectively). We examined personal 24-h PM2.5 exposure levels and DNA damage levels in peripheral blood lymphocytes for each subject. We found that the variant allele of rs12199241 in AIMP3 was significantly associated with DNA damage levels (β=0.343, 95%CI: 0.133-0.554, P=0.001). Meanwhile, the results of rs5030754 in EPRS and rs3784929 in KARS indicated their suggestive roles in DNA damage processes (β=0.331, 95%CI: 0.062-0.599, P=0.016 for rs5030754; β=0.192, 95%CI: 0.016-0.368, P=0.033 for rs3784929, respectively). After multiple testing, rs12199241 was still significantly associated with DNA damage levels. Combined analysis of these three polymorphisms showed a significant allele-dosage association between the number of risk alleles and higher DNA damage levels (Ptrend<0.001). These findings indicate that genetic variants in MSC genes may account for PM2.5-modulated DNA damage levels in Chinese populations.<br /> (Copyright © 2016. Published by Elsevier B.V.)
- Subjects :
- Alleles
China
Comet Assay
DNA Repair
Databases, Genetic
Gene Frequency
Genotyping Techniques
Humans
Lymphocytes metabolism
Lysine-tRNA Ligase genetics
Peptide Elongation Factors genetics
Polymorphism, Single Nucleotide
Tumor Suppressor Proteins genetics
Amino Acyl-tRNA Synthetases genetics
Asian People genetics
DNA Damage
Genetic Variation
Subjects
Details
- Language :
- English
- ISSN :
- 1873-135X
- Volume :
- 786
- Database :
- MEDLINE
- Journal :
- Mutation research
- Publication Type :
- Academic Journal
- Accession number :
- 26871430
- Full Text :
- https://doi.org/10.1016/j.mrfmmm.2016.01.006