Open AccessImpact of natriuretic peptide polymorphisms on diastolic and metabolic function in a populational cohort: insights from the STANISLAS cohort
Author(s) -
Xhaard Constance,
Rouget Raphaël,
Vodovar Nicolas,
Le Floch Edith,
DandineRoulland Claire,
Wagner Sandra,
BacqDaian Delphine,
Thuillier Quentin,
Boivin JeanMarc,
Branlant Christiane,
Deleuze JeanFrançois,
BehmAnsmant Isabelle,
Zannad Faiez,
Rossignol Patrick,
Girerd Nicolas
Publication year - 2022
Publication title -
esc heart failure
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.787
H-Index - 25
ISSN - 2055-5822
DOI - 10.1002/ehf2.13674
Subject(s) - medicine , single nucleotide polymorphism , genome wide association study , natriuretic peptide , heritability , cohort , candidate gene , methylenetetrahydrofolate reductase , brain natriuretic peptide , cardiology , endocrinology , heart failure , genetics , biology , gene , allele , genotype
Aims Elevated brain natriuretic peptide (BNP) and the N‐terminal fragment of its pro‐hormone (NT‐proBNP) have become established biomarkers for heart failure and are associated with cardiovascular morbidity and mortality. Investigating sources of inter‐individual heterogeneity, particularly genetic factors, could help better identify patients at risk of future cardiovascular disease. The aim of this study was to estimate the heritability of circulating NT‐proBNP levels, to perform a genome‐wide association study (GWAS) and gene‐candidate analysis focused on NPPB–NPPA genes on these levels, and to examine their association with cardiovascular or metabolic outcomes. Methods and results A total of 1555 individuals from the STANISLAS study were included. The heritability of circulating NT‐proBNP levels was estimated at 15%, with seven single nucleotide polymorphisms (SNPs) reaching the significant threshold in the GWAS. All above SNPs were located on the same gene cluster constituted of MTHFR , CLCN6 , NPPA , NPPB , and C1orf167 . NPPA gene expression was also associated with NT‐proBNP levels. Moreover, six other SNPs from NPPA–NPPB genes were associated with diastolic function (lateral e′ on echocardiography) and metabolic features (glycated haemoglobin). Conclusions The heritability of natriuretic peptides appears relatively low (15%) and mainly based on the same gene cluster constituted of MTHFR , CLCN6 , NPPA , NPPB , and C1orf167 . Natriuretic peptide polymorphisms are associated with natriuretic peptide levels and diastolic function. These results suggest that natriuretic peptide polymorphisms may have an impact in the early stages of cardiovascular and metabolic disease.