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

Autophagy associated genes (ATGs) played an important role in the repair process of DNA damage and decreased autophagy may weaken the repair process and aggravate DNA damage. Based on this, we hypothesized that DNA damage levels might be modified by genetic variants in autophagy associated genes. In order to validate our hypothesis, 307 subjects were recruited from three different cities (Zhuhai, Wuhan and Tianjin) in China. Demographic data, individual 24-h PM _2.5 exposure and peripheral blood DNA damage levels were also detected. Seven potentially functional polymorphisms in four essential autophagy associated genes (ATG5, ATG7, ATG8 and ATG13) were screened to evaluate the relationship between the polymorphisms of autophagy associated genes and DNA damage levels. This association was assessed by using multivariable linear regression model, age, sex, smoke and PM _2.5 exposure levels were adjusted in each city. We found that rs12599322 in ATG8 (A>G, β=0.263, 95% CI: 0.108-0.419, P=8.98×10 ^-4 ) and rs7484002 in ATG13 (A>G, β=0.396, 95% CI: 0.085-0.708, P=0.013) were significantly associated with higher DNA damage levels. Furthermore, functional annotations showed that both rs12599322 and rs7484002 located at transcription factor binding sites (TFBS), indicating that they could regulate the expression of related genes through TF regulation. Following allelic trend analysis revealed that the DNA damage levels were significantly aggravated with the increasing number of risk variants in autophagy associated genes (P for trend: 8.09×10 ^-5 ). Our findings suggested that the polymorphisms in ATGs may influence DNA damage levels in one of the Chinese population.
(Copyright © 2017. Published by Elsevier B.V.)