Abstract
DNA damage and subsequent repair pathways have been involved in the initiation and progression of atherosclerosis. Meiotic recombination 11 homolog A (MRE11A) gene polymorphisms have been associated with the presence of myocardial infarction. We analyzed five MRE11A gene polymorphisms in 386 individuals with subclinical atherosclerosis and 1093 healthy controls. Under different models, the rs13447720 (Odds ratio = 0.646, Padditive = 0.009; Odds ratio = 0.636, Pdominant = 0.012; Odds ratio = 0.664, Pover–dominant = 0.025; Odds ratio = 0.655, Pcodominant1 = 0.021) and rs499952 (Odds ratio = 0.807, Padditive = 0.032; Odds ratio = 0.643, Pcodominant2 = 0.034) polymorphisms were associated with a lower risk of subclinical atherosclerosis. On the other hand, the rs2155209 polymorphism was associated with a reduced risk of having a coronary artery calcification score ≥ 100 Agatston units. The rs13447720, rs499952, and rs2155209 polymorphisms, as well as the haplotypes that included the five studied polymorphisms were associated with some clinical and metabolic parameters in both subclinical atherosclerosis and healthy individuals. Our results suggest that the rs13447720 and rs499952 polymorphisms are associated with a decreased risk of developing subclinical atherosclerosis, whereas the rs2155209 is associated with a lower subclinical atherosclerosis severity (coronary artery calcification < 100 Agatston units). MRE11A polymorphisms and haplotypes were associated with clinical and metabolic parameters.
Highlights
Atherosclerosis is a progressive and multifactorial disease conditioned by genetic and environmental factors and characterized by the accumulation of lipids in the intima and middle arterial layers
The results showed the association of the rs2155209 polymorphism of the meiotic recombination 11 homolog A (MRE11A) gene with the presence of myocardial infarction (Verschuren et al, 2013)
This study evaluated the association of these polymorphisms with a severe state of atherosclerosis; we decided to evaluate the role of the same polymorphisms in early-stage atherosclerosis
Summary
Atherosclerosis is a progressive and multifactorial disease conditioned by genetic and environmental factors and characterized by the accumulation of lipids in the intima and middle arterial layers. MRE11A Polymorphisms and Subclinical Atherosclerosis deoxyribonucleic acid (DNA) damage and subsequent repair pathways are increasingly recognized as a causal factor for the genesis and progression of atherosclerosis (Shah and Mahmoudi, 2015). A recent genome-wide association study analyzed common genetic variants in five DNA repair pathways in two independent cohorts (Verschuren et al, 2013). The aim of the present study was to analyze the distribution of MRE11A polymorphisms in asymptomatic individuals with subclinical atherosclerosis (SA)– defined as a coronary artery calcification (CAC) score greater than zero–in order to establish its role in early atherosclerosis. We selected the five polymorphisms which had been previously analyzed in individuals with myocardial infarction in the genome-wide association study (Verschuren et al, 2013)
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