Apolipoprotein A1-75bp And+83bp Gene Polymorphisms In The Risk For Dyslipidemia And Coronary Artery Disease

Backgroud:Atherosclerotic coronary heart disease (CHD) is considered as myocardial ischemia, hypoxia or necrosis caused by vascular stenosis or occlusion occurs in the coronary artery atherosclerotic lesions. Since the beginning of the60s of the last century, people have recognized that dyslipidemia is the important risk factor for atherosclerosis. Statins can significantly reduce the incidence of cardiovascular events by lowering low-density lipoprotein (LDL) levels. Besides, it plays a very important role in anti-inflammatory, vascular endothelial protection, anti-platelet aggregation, stabilize plaque and anti-vascular atherosclerosis and other effects in the prevention and treatment of cardiovascular diseases. However, in the clinical practice, strengthening the high-dose statin therapy based on our current lipid management guidelines, the patients still left high residual cardiovascular risk. Thus, it is expected to further reduce cardiovascular risk by controlling the traditional cardiovascular risk factors and the residual cardiovascular risk. Number of clinical studies showed that the risk of coronary events with low high density lipoprotein (HDL) group was significantly higher compared to that with the higher levels of HDL. Thus, low HDL becomes a major risk of residual cardiovascular risk. Apolipoprotein Al (apoAl) is the major structural protein in plasma HDL particles, which can reflect the determination of the level of HDL. ApoAl and HDL receptors can activate lecithin cholesterol acyltransferase (LCAT) and cholesterol esterification. Additionally, it participates in reversing cholesterol transportation from peripheral cells back to the liver to be first-past metabolised. Meanwhile apoAl also plays important roles in anti-inflammatory, antioxidant, protecting vascular endothelium and anti-atherosclerosis and so on. Clinical studies also have confirmed that the value of apoAl in diagnosing coronary artery disease was much more reliable than HDL. ApoAl gene polymorphism has3SNP:-75G/A,+83C/T and+84G/A. apoAl gene-75bp and+83bp polymorphism may affect the lipid profile of people, and even affect the effect of the statin therapy. This site not only has a negative relationship with HDL, but also has a positive relationship with the elevated levels of apoAl. Besides, ApoAl gene polymorphisms may prove to be protective factors to coronary artery disease (CAD). Studies have found that patients with apoAl GG/CC gene could reduce the risk of coronary heart disease. Instead, patients who carried with CT/GA gene got higher risk for coronary heart disease. However, results of the studies in China differed. Therefore, based on the above controversy, it needs to further study about ApoAl-75bp and+83bp gene polymorphisms in the risk for dyslipidemia and coronary artery disease.Objective:Aimed to explore the relationship between the effects of apolipoprotein apoA1-75bp and+83bp polymorphism on lipid profile, and with the severity of CAD.Method:624patients were enrolled from2011to2012in Guangdong General Hospital (Guangzhou, China). They were subdivided into two groups according to the result of coronary angiography (CAG):CAD group and non-CAD group. General data were analysed including the profiles of lipids,-75bp and+83bp polymorphisms and Gensini scores to determine the correlation between lipids,-75bp and+83bp polymorphisms with CAD. The statistical analysis was performed with the SPSS13.0software program. Continuous data was presented as mean±SD, and compared by the Student’s test when data was normally distributed, otherwise compared by the Wilcoxon rank-sum test. Categorical data was presented as percentage and compared by χ2test. Univariate analysis and multiple logistic regression analysis were used to simultaneously analyse the influence of multiple factors on CAD and the severity of CAD. A variable was identified as a significant independent factor when the p value was<0.05.Results:624patients with mean age of61.9±10.3years were screened including401patients in CAD group and223patients in non-CAD group. The results including:1). The status of TC, TG, LDL, apoB, apoAl and HDL levels showed statistically significant difference between both groups (P<0.05).2). Comparison between apoAl-75bp and+83bp gene polymorphisms and lipid profile:in the CAD group, the levels of HDL, apoAl in the mutant-type (GA/AA) was higher than that in the wild-type (GG), the difference was statistically significant (P<0.005). Meanwhile, the levels of HDL, apoAl in the mutant-type (CT) was higher than that in the wild-type (CC), the difference was also statistically significant (P<0.005). In non-CAD group:the levels of HDL, apoAl in the mutant-type (GA/AA or CT) was higher than that in the wild-type (GG/CC), but there was no statistically significant difference (P>0.05). The remaining lipid parameters showed no statistical difference.3). Association between apoA1-75bp and+83bp polymorphism with CAD:CAD patients carrying the lower frequency of A allele, compared with the non-CAD group (43.1%vs53.4%, P=0.014). In this study, apoAl+83gene analysis did not find TT genotype. And the CT genotype frequencies in CAD group was lower than that in the non-CAD group (10.7%vs17.9%, P=0.01).4). Association between apoA1M1and M2polymorphism with Gensini score. Combined with Gensini score, the selected patients were divided into four groups:including Gensini score=0in32patients, Gensini score=0-30in104patients, Gensini score=30-60in112patients, Gensini score>60in123patients. With increasing score, A or T allele (GG/GA or CT) was significantly reduced (61.6%>49.5%>45.5%>39.7%, P=0.011;24.7%>15.8%>10.8%>8.8%, P=0.004). The apoA1-75bp and+83bp polymorphism had substantial relationship with the severity of CAD (P<0.005). Multivariate logistic regression analysis showed that the-75bp site mutant (AA/GA)(OR=0.673, P=0.030) and+83bp site mutant (CT)(OR=0.507, P=0.009) are independent protective factor for coronary heart disease.Conclusion:We conclude that apoA1-75bp and+83bp polymorphism had substantial relationship with the lipids and the severity of CAD. Integration of apoA1polymorphism may be valuable for risk evaluation of CAD.