Coronary artery disease is characterized by an inflammatory status and it represents the major cause of death in elderly . In Tunisia, the allele and genotype frequencies of Hsp70-2 were observed in several studies [12, 19, 20] which evaluated a highly significant association between polymorphisms in Hsp70 gene and studied diseases.
In this study we show for the first time the association between lipid profiles, polymorphism PstI site of Hsp70–2 gene and CAD. Biochemical analysis results showed a decreased level of ApoA- and HDL and inversely an increased level of total cholesterol, triglyceride, Apo B and hs-CRP in patients with CAD compared with control group.
Furthermore, a significant correlation of elevated level of some biochemical parameters with CAD was explained by different mechanisms: Elevated levels of LDL cholesterol are associated with an increased risk of coronary heart disease, stroke, and peripheral artery disease. LDL lipoprotein deposits cholesterol along the inside of artery walls, causing the formation of cholesterol plaque. This accumulation causes thickening of the artery walls and narrowing of the arteries which decreases blood flow through the narrowed area .
In addition, elevated levels of C-reactive protein (CRP), a protein that appears in the bloodstream during many inflammatory processes, are associated with acute coronary events. CRP may be used as a predictor of cardiovascular disease based on its correlation with the other known cardiac risk factors and their role in the formation of atherosclerosis .
Controversial studies regarding the role of Apo A-I as a risk factor of CAD. Indeed, same studies found a positive correlation but others did not .
Additionally, P2-CAD patients displayed increased total serum cholesterol, TG and hs-CRP in comparison to P1-CAD patients (Additional file 3: Table S3), while no differences were observed in serum ApoA-I and HDL between P2/P2 and P1/P1 patients, (Additional file 3: Table S3). Accordingly, patients with P2/P2 genotype are more predisposed to plaque accumulation than those with the P1/P1 genotype and are at risk for possible acute coronary events and the progression of CAD.
However, Hsp70-2 polymorphism does seem to affect hs-CRP (Additional file 3: Table S3). The specific role of Hsp70 within the plaques is still unclear and the data are contradictory. A positively correlation was found between serum HSP70 and asymmetric dimethylarginine (ADMA) with high hs-CRP levels in type 2 diabetes patients suggest that both ADMA and HSP70 have similarly an inhibitory function on nitric oxide synthase (NOS) in inflammatory and oxidative stress situation . In addition molecular analysis of a polymorphic PstI site of Hsp70–2 gene lying in the coding region at position 1267 of the Hsp70-2 gene have revealed that the heterozygous P1/P2 genotype was significantly more frequent in patient group and control patient. The homozygous P2/P2 genotype was significantly more frequent in patient group and significantly less frequent in control group (Additional file 2: Table S2). Our results are consistent with results reported in the literature . Patients with P2 genotype are more predisposed to atheromatous plaque accumulation within the walls of the coronary arteries than those with the P1 genotype and are at risk for possible rupture and start limiting blood flow to the heart muscle .
Our report highlighted a direct correlation between P2–Hsp70-2 homozygous, elevated level of LDL cholesterol, hs-CRP and CAD. Therefore, a higher significant association was found in patients group compared with controls. Other studies indicate the association of high Hsp70 levels with low CAD risk. The inverse relation between Hsp70 serum levels and CAD are conjectural . This study suggest that the serum level of HSP70 protein is a potent marker for lowered CAD susceptibility and may be helpful, along with other currently recognized risk factors, in more accurately conveying the overall risk of an individual for CAD . Our data seem to suggest that the presence of 1267 Hsp70–2 polymorphism in patients with CAD play a detrimental role in the accumulation of plaques and the formation of atherosclerosis.
The expression level of Hsp70–2 gene could be among factors affecting the regulation of cholesterol rate or other mechanisms exacerbating this step. It has been shown that Hsp70–2 plays a role in the route of synthesis of cholesterol, folding and subcellular localization of hs-CRP protein. Further studies involving larger patient populations will be required to confirm this hypothesis.