5-Lipoxygenase Activating Protein Gene Variants And Coronary Heart Disease: A SNP Association Study

Objectives:5-Lipoxygenase(5-LO)/5-Lipoxygenase-Activating Protein (FLAP)pathway has been independently implicated in the pathogenesis of athrosclerosis.When the pathway activated,leukotriene are released,it can increase cardiovascular permeability,stimulate sustained smooth muscle contraction,induced monocyte adhesion to the vascular endothelium.,and plays a role in atherogenesis. Association and linkage studies showed polymorphism of SNPs in ALOX5AP gene as a susceptibility gene for myocardial infarction(MI)and stroke by genomewide scan studies.To date,no genetic-epidemiological data about coronary artery disease(CHD) are available for populations in the Han nationality.The aim of this study was to explore the role of variants of gene encoding arachidonate 5-lipoxygenase-activating protein as possible susceptibility factors for CHD.and myocardial infarction(MI)in patient with or without angiographyically proven CHD in the Han nationality of tianjin,China.Methods:A case-control design was applied in this study,we recruited 282 unrelated Chinese inpatients with CHD(mean age62.4±10.6,male 164,female 187)in the Affliated Hospital of Medical College of Armed Police Forces between July and December 2007,the disease severity was evaluated by counting number of major epicardial coronary arteries(left anterior descending,circumflex,and right)affected with≥1 significant stenosis(≥50%).CHD subjects were classified into MI and non-MI subgroup by combining data from history with a thorough review of medical records showing diagnostic electrocardiogram and enzyme changes.On the other hand,79 subjects(mean age 56.7±8.6,male 30,female 49)had completely normal coronary arteries,being submitted to coronary angiography for reasons other than CHD,mainly valvular heart disease and cardiomyopathy(CHD-free group),contral were also to have neither history nor clinical or instrumental evidence of atherosclerosis in vascular district beyond the coronary bed.ALOX5AP 2354T/A and 16699A/G was genotyped by restriction fragment length polymorphism analysis for all the samples.Quantitative data were assessed using the Student's t-test.Associations between qualitative variables were analysed with the x~2 test or Fisher exact test,when indicated.Multivariate logistic regression model was used to exclude the influence of confounding factors and determine the interaction among polymorphisms on the risk of CHD or MI.Statistical analysis was conducted using the SSPS.Pairwise linkage disequilibrium and Haplotype frequencies was estimated using SHEsis software. (http://analysis.bio-x.cn/my Analysis.php)Results:1 The common clinical feature of 282 CHD and 79 non-CHD patients are separately displayed in table 2.It can be seen that male,age,percentages of smoking, systolic pressure,high density lipoprotein were significantly different among the CHD group and non-CHD group(P＜0.05),however,BMI,hypertension,diabetes,CHD family history,diastolic pressure,fasting plasma levels of glucose,total cholesterol,low density lipoprotein and triglycerides were not significantly different among the CHD and non-CHD patients(P＞0.05).2 Minor allele frequencies of 2354T/A and 16699G/A were 28.5%and 2.5%in the Han nationality of tianjin,China.The genetype frequency of 2354T/A TT,TA,AA are 54.4%,34.2%,11.4%,The genetype frequency of 16699G/A 96.2%,2.5%, 1.3%.There is no linkage disequilibrium between 2354T/A and 16699G/A.3 In univariate analysis,polymorphism of 2354T/A and 16699A/G was no significantly different between case and control group(P＞0.05).Multivariate analysis also indicated no relationship between polymorphism of 2354T/A,16699A/G and CHD.4 Haplotype analysis showed that the most frequent haplotypes were the AG 28.6%,TG 68.9%,Whereas,haplotype analysis showed there is no difference of haplotye between case and control group(P＞0.05).5 Furthermore,subgroups were divided according to the phenotype including Myocardial infarction(MI)and non-Myocardial infarction(non-MI).Univariate analysis showed 16699A/G might be a protective factor.However multivariate analysis showed there was no polymorphism associated with MI.Both univariate and multivariate analysis showed no relationship between SNP and CAD severity.Conclusion:The present investigation in the Han nationality provides no evidence that the ALOX5AP gene might play a role in conferring susceptibility or severity to CHD.