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

- We examined the association of genetic variants in SMARC genes with DNA damage levels.
- Twenty polymorphisms in five SMARC genes were analyzed in 307 healthy Chinese subjects from southern, central and northern China.
- The genotypes of rs6857360 in SMARCA5, rs6919 and rs2727280 in SMARCD2, and rs17173769 in SMARCD3 were significantly associated with DNA damage levels.
- A locus-dosage effect was observed between combined genotypes of SMARC genes and DNA damage levels.

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.