The Relationship Between Lipoprotein(a), Its Single Nucleotide Polymorphims And Calcific Aortic Valve Disease

The aim of the study: Degenerative calcific aortic valve disease is one of the common conditions that formed in the elderly predominantly. The aim of the study was to detect the relationship between either plasma lipoprotein(a) or its single nucleotide polymorphisms(SNPs) and degenerative calcific aortic valve disease, in order to further explore the initiating agents and the influene of SNPs to valve degeneration.Method: A total of 185 consecutive CAVD patients( age≧50 years) who had been admitted to the author’s cardiology department ward was enrolled in 2011 to 2013. The control group consisted of 171 non-CAVD subjects with matched age and gender. The basic clinical data were collected, then the samples of venous blood were obtained in the morning after an overnight fast. Serum total cholesterol, triglyceride,high-density-lipoprotein cholesterol, low-density-lipoprotein cholesterol, uric acid, serum calcium, serum phosphate and plasma lipoprotein(a) were measured. The statistic analysis was conducted between the two groups, the multiple Logistic regression was used for the correlation analysis between the risk factors and CAVD. The CAVD group was divided into four subgroups by aortic peak velocity: aortic valve sclerosis, mild calcific aortic valve stenosis(CAVS), medium CAVS and severe CAVS. The statistic analysis was conducted for experimental data(TC, LDL-C, Lp(a)) and ultrasonic parameter( left ventricular diastole diameter, left ventricular wall thickness,and left ventricular ejection fraction) between the four subgroups. Then the samples of venous blood were obtained from 164 CAVD patients and 164 control subjects. All the samples were conducted genotype detection using Hot Star Taq multiple PCR technology, Gene Mapper4.1 was used to confirm the SNP typing. The statistic analysis was conducted between the two groups’ genotypes, and the correlation analysis between the genotypes and phenotypes.Results: Compared to the controls, patients with CAVD had higher plasma levels of LP(a),Serum TC and LDL-C. Other traditional risk factors were similar between two groups. Multiple Logistic regression analysis identified plasma levels of LP(a) as independent determinant of CAVD(P<0.001). The plasma Lp(a) levels had no difference between the subgroups of CAVD. The data of echocardiography showed that the left ventricular diastole diameter and the ventricular wall thickness in the medium and severe CAVS subgroup were bigger than the other two subgroups, howerer the left ventricular ejection fraction were lower than the other two subgroups, the difference was significant. LPA gene mutation included rs10455872, rs6415084, rs3798221 and rs7770628. Genotypes of rs10455872 were AG, AA, rs6415084 were CT, CC and TT, rs3798221 were GT, GG and TT, rs7770628 were CT, CC and TT. Except rs3798221, the cases, alleles frequencies and Lp(a) in blood of rs10455872, rs6415084 and rs7770628 genotypes had significantly differences(P<0.05). Rs10455872, rs6415084, rs7770628, Lp(a) and aortic valve disease were closely related(P<0.05).Conclusion: High plasma levels of LP(a) are independent predictors of the CAVD progression. LPA gene polymorphism(rs10455872, rs6415084 and rs7770628) and the plasma Lp(a) play very important roles in the occurrence and development of CAVD, LPA gene may be a susceptible gene.