Association of brain natriuretic peptide gene polymorphisms with chronic obstructive pulmonary disease complicated with pulmonary hypertension and its mechanism

Abstract

Objective: To examine the association between brain natriuretic peptide (BNP) gene single nucleotide polymorphisms (SNPs) and chronic obstructive pulmonary disease (COPD) and COPD with pulmonary hypertension (PH) and to analyze its mechanism. Methods: The genotypes of BNP at the rs198389, rs6668352, and rs198388 loci in 339 patients with COPD (205 in the COPD/PH− group and 134 in the COPD/PH+ group) and 125 healthy subjects were detected by PCR/Sanger sequencing. The serum levels of BNP, fibrinogen (Fbg), and Apelin were measured in all subjects by ELISA. Results: The BNP rs198389 locus G allele, rs6668352 locus A allele, and 198388 locus T allele were high risk factors for COPD (P<0.001). Logistics regression analysis showed that BNP rs198389 locus G allele, rs6668352 locus A allele, and rs198388 locus T allele were high risk factors for PH in COPD patients (all P<0.001). The levels of the serum BNP and Fbg protein in the control group, COPD/PH− group, and COPD/PH+ group increased successively, and the expression levels of Apelin protein decreased successively (all P<0.001). The BNP and Fbg protein levels in the wild-type, heterozygote, and mutant homozygote in BNP rs198389, rs6668352, and rs198388 loci increased successively, and the serum Apelin protein levels decreased successively (all P<0.001). Conclusion: The polymorphisms of BNP at the rs198389, rs6668352, and rs198388 loci are associated with the occurrence of COPD and COPD with PH, and the occurrence may be related to the abnormal expression level of BNP, Fbg, and Apelin protein in the serum.

Genetic association analysis of the cardiovascular biomarker: N-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP)

“…We identified rs632793 as the most significant and consistent genetic variant associated with NT-proBNP level in the total LLFS, as well as, in the proband generation alone. This is in line with previous studies [14,16,27,28], although, some other studies focused specifically and solely on rs198389 [15,16,24,[29][30][31]. These two variants are in strong LD in our study (Fig 1) and; thus, likely represent the same underlying genetic signal.…”

The association between apelin polymorphisms and hypertension in China: A meta-analysis

“…23,24 Four studies not associated with apelin polymorphisms were excluded. 25–28 Six studies not suitable for hypertension study were excluded. 14,19,25,29–33 Two studies only included other apelin polymorphisms were excluded.…”

“…25–28 Six studies not suitable for hypertension study were excluded. 14,19,25,29–33 Two studies only included other apelin polymorphisms were excluded. 18,19 Six studies were excluded, from which appropriate data cannot be extracted.…”

Novel TNIP2 and TRAF2 Variants Are Implicated in the Pathogenesis of Pulmonary Arterial Hypertension

“…For example, variants in the endoglin gene are linked with PAH associated with connective tissue disease (44), polymorphisms in estrogen-related genes may impact the risk of portopulmonary hypertension (45), and SOX17 have been implicated in PAH associated with congenital heart disease (41). Also, variants in CAV1, TRPM8, and BNP have been linked with PH secondary to chronic obstructive pulmonary disease (46)(47)(48). These findings underscore the importance of expanding our genetic sequencing application to PH populations not traditionally thought to have a genetic predisposition.…”