Correlation Of Lp(a)Gene Polymorphism With Elderly Patients With Degenerative Heart Valve Disease In Han Chinese Population In The Peninsula Region

Objective:Senile degenerative valvular heart disease is a chronic progressive disease that leads to arrhythmia,thromboembolism,left ventricular dysfunction,and even sudden death when the valves are severely calcified and stenotic.Studies at home and abroad have found that lipoprotein(a)in plasma is mainly regulated by LPA gene.LPA gene is located on the long arm of chromosome 6(6q26-27).Single nucleotide polymorphism(SNP)at LPA gene locus is closely related to the expression of plasma Lp(a).With the aging population,the elderly population with degenerative valvular heart disease will inevitably increase rapidly,so it is necessary to further explore the association between LPA SNPs and elderly patients with degenerative valvular heart disease in the Han population in the peninsula.Methods:1.295 patients aged ≥60 years who were hospitalized at XXX from August 1,2021 to December 3,2022 were selected.According to the results of echocardiography,the subjects were divided into degenerative valvular heart disease group and non-degenerative valvular heart disease group.According to the grading criteria of valvular calcification,degenerative valvular heart disease was divided into mild calcification group,moderate calcification group and severe calcification group.2.Collect the following clinical data of patients:(1)general data:age,gender,BMI,blood pressure,past medical history,smoking and drinking history;(2)laboratory parameters:FBG、Lp(a)、TC、LDL-C、HDL-C、TG、BUN、GFR、Ca、P、RBC、HCT、RDW-CV、Hb、Plt、MPV、NT-ProBNP、D-D;(3)echocardiographic parameters:LVDd、LVDs、EDV、LVEF、TAPSE、PASP、E/e’.3.Through NCBI dbSNP database,three SNPs related to Lp(a),rs 10455872,rs 7765803 and rs 1800769,were selected and genotyped by Mass Array SNP typing technique.4.SPSS 26.0 software was used for statistical analysis.The measurement data obeying normal distribution were expressed as ±s,and independent sample t test was used for comparison between groups;the measurement data not obeying normal distribution were expressed as M(Q25,Q75),and rank sum test was used for comparison between groups.Enumeration data were expressed as n(%)and compared between groups using the 2 test;when the outcome variables of the R×C contingency table were multivariate ordinal,rank sum test was used for comparison between groups.Hardy-Weinberg equilibrium tests were performed for the included SNP loci,and P>0.05 was considered consistent with Hardy-Weinberg equilibrium.Genotype frequencies and allele frequencies were obtained by direct counting,and comparisons of genotypes or alleles between groups were performed using the chi-square test.Multivariate logistic regression was used to analyze the effect of each genotype and allele on the incidence of SDHVD under clinical data and dominant model.P<0.05 was considered statistically significant.Results:1.General condition of the study subjectsA total of 295 subjects were included in this study,191(64.75%)in the non-SDHVD group and 104(35.25%)in the SDHVD group.According to the grading criteria of cardiac valve calcification,SDHVD was divided into three subgroups:38 patients(12.88%)in the mild calcification group,55 patients(18.64%)in the moderate calcification group,and 11 patients(3.73%)in the severe calcification group.2.Comparison of clinical data between SDHVD and non-SDHVD patientsAge,diabetes,hypertension,FBG,Lp(a),RBC,HCT,Hb,NT-ProBNP,E/e’ were significantly different between the two groups(P<0.05);there were no significant differences in gender,BMI,systolic blood pressure,diastolic blood pressure,mean arterial pressure,history of smoking and drinking,coronary heart disease,hyperlipidemia,TC,TG,LDL-C,HDL-C,BUN,GFR,Ca,P,RDW-CV,Plt,MPV,D-dimer,LVEF,EDV,LVDd,LVDs,TAPSE,and PASP between the two groups(P>0.05).3.Comparison of clinical data between SDHVD subgroups and non-SDHVD groupsAge,hypertension,Lp(a),MPV,NT-proBNP and E/e’ were significantly different among the four subgroups(P<0.05).Post-hoc pairwise comparisons showed that age and Lp(a)were associated with the severity of valvular calcification,and there were significant differences among the four subgroups(P<0.05);hypertension and E/e’ were significantly different between the moderate calcification group and the non-SDHVD group(P<0.05);after Bonferroni correction,MPV and NT-proBNP were not significantly different among the four subgroups(P>0.05).4.Multivariate logistic regression analysis of independent risk factors affecting SDHVDThe results of multivariate logistic regression analysis showed that age(OR=1.196,95%CI:1.093～1.310),Lp(a)(OR=1.016,95%CI:1.010～1.021),and E/e’(OR=1.200,95%CI:1.024～1.407)were independent risk factors for SDHVD(P<0.05).5.Association analysis of LPA gene polymorphisms and SDHVDGenotype distributions of the included LPA SNPs(rs 10455872,rs 7765803,rs 1800769)were in accordance with Hardy-Weinberg equilibrium(P>0.05).The results of the 2 tests showed that there were significant differences in the distribution frequencies of rs 7765803 genotype and allele C between the two groups(P<0.05).There was no significant difference in the distribution of rs 10455872 and rs 1800769 genotypes and alleles between the two groups(P>0.05).Multivariate logistic regression analysis was used to adjust the effects of age,gender,Lp(a),and E/e’ to analyze the effects of different genotypes and alleles on the incidence of SDHVD under the dominant model,and the results showed that age(OR=1.125,95%CI:1.051～1.204),Lp(a)(OR=1.015,95%CI:1.010～1.019),E/e’(OR=1.175,95%CI:1.017～1.359),and rs 1800769 TT+CT genotype(OR=2.741,95%CI:1.246～6.031)were closely related to SDHVD(P<0.05).rs 10455872 and rs 7765803 were not significantly associated with SDHVD(P>0.05).Conclusion:1.Age was an independent risk factor for SDHVD,and Lp(a)and E/e’ might be independent risk factors for SDHVD.2.Under the dominant gene model,the risk of rs1800769 TT+CT genotype SDHVD was 2.741 times higher than that of CC genotype,and the increase of rs1800769 T allele may be an independent risk factor for SDHVD.3.Lp(a)level is associated with the pathogenesis of SDHVD,and LPA gene polymorphism(rs 1800769)is closely related to the occurrence of SDHVD and may be a susceptibility gene for the occurrence of SDHVD.