The Relationship Between Serum N-terminal Pro-brain Natriuretic Peptide Levels And Related Gene Mutations And Blood Pressure

Part I:The Relationship between BP,BPV and NT-proBNP in Failure Patients Background and ObjectiveTo evaluate the association between blood pressure(BP),the blood pressure variability(BPV)and the plasma N terminal pro B type natriuretic peptide(NT-proBNP)concentration in moderate and severe heart failure patients with preserved left ventricular ejection fraction(HFpEF).Subjects and MethodsWe enrolled a total of 72 moderate and severe heart failure patients who accepted 24-hour ambulatory blood pressure monitoring(ABPM)in Fuwai hospital.The plasma NT-proBNP concentration was detected by electrochemiluminescence immunoassay.Then the relationship between BP,BPV and plasma NT-proBNP concentration was analyzed.Results(1)Patients with higher NT-proBNP level had significant lower level of systolic blood pressure(SBP),diastolic blood pressure(DBP)and diastolic blood pressure variability(DBPV)(P<0.05).(2)The conversion value of plasma NT-proBNP concentration had significant linear negative correlation to SBP,DBP,and DBPV and the correlation indexes respectively are-0.375,-0.382 and-0.371(P<0.01).(3)Multiple linear regression analysis showed that the conversion value of plasma NT-proBNP still significantly and negatively correlated to DBPV after adjusted for sex,age,body mass index,DBP and history of hypertension(P<0.05).ConclusionsThere was a negative relationship between SBP,DBP,DBPV and plasma NT-proBNP concentration in moderate and severe HFpEF patients,and they may be useful to reflect the condition of heart failure to some extent.Part ?The Associations of NT-proBNP related genetic variation with longitudinal blood pressure changes and incident hypertension in Chinese Han populationBackground and ObjectiveWe further analyzed the relationship between NT-proBNP related gene variation and blood pressure level.Previous GWAS studies found that the genetic variants of NPPB and KLKB1 affected serum BNP and NT-proBNP levels.Based on family follow-up and cohort research data,we examined the associations of single nucleotide polymorphisms(SNPs)in NPPB and KLKB1 genes with longitudinal blood pressure changes and hypertension incidence.Subjects and MethodsThe subjects of this study were mainly from the Genetic Epidemiology Network of Salt Sensitivity(GenSalt)and a part of the International Collaborative Study of Cardiovascular Disease in Asia(InterASIA).A total of 3809 subjects with available blood pressure and genotype information were eligible for the current study including 1906 participants from GenSalt study,1903 participants from InterASIA study.According to the purpose of the study,19 tag SNPs from NPPB and KLKB1 and 11 KKS related genes were selected for analysis.We examined the associations of selected SNPs with longitudinal blood pressure changes using a generalized linear mixed-effects model.We further assessed the associations of selected SNPs with incident hypertension using generalized linear mixed-effects model for the GenSalt study and logistic regression for the InterASIA study.Finally,gene-based analyses were conducted using truncated product method(TPM)to evaluate the associations of KKS-related genes with longitudinal blood pressure changes and the incidence of hypertension.ResultsThe relationships between two SNP loci rs4253308 and rs4253295 in KLKB1 and longitudinal DBP changes during follow-up in the GenSalt study were statistically significant(P =0.003,0.005 respectively).In the InterASIA study,four SNPs near KLKB1 gene,rs4241821,rs3087505,rs2221843,and rs3822055,were significantly associated with incident hypertension(P =0.010,0.009,0.004,0.009 respectively)with OR values ranging from 1.6 to 1.8.In a gene-based association analysis,the associations of KLKB1,MME,and SERPINA4 with longitudinal DBP changes were found to be statistically significant(P =0.0002,0.0019,<0.0001)in the GenSalt study.In the InterASIA study,multiple sites of KLKB1 as a whole were associated with the onset of hypertension(P<0.0001).ConclusionsWe found that common variants in KLKB1 gene and KKS-related geneswere associated with longitudinal blood pressure changes and the incidence of hypertension in Chinese population,providing new evidence for KLKB1 as well as KKS-related genes and its role in the regulation of blood pressure.Further studies are required to replicate these associations in independent samplesand to explore the specific regulatory mechanisms affecting blood pressure changes and incident hypertension.