Natriuretic peptide system gene variants are associated with ventricular dysfunction after coronary artery bypass grafting - PubMed (original) (raw)

Multicenter Study

. 2009 Apr;110(4):738-47.

doi: 10.1097/aln.0b013e31819c7496.

Charles D Collard, Stanton K Shernan, Christine E Seidman, Jonathan G Seidman, Kuang-Yu Liu, Jochen D Muehlschlegel, Tjorvi E Perry, Sary F Aranki, Christoph Lange, Daniel S Herman, Thomas Meitinger, Peter Lichtner, Simon C Body

Affiliations

Multicenter Study

Natriuretic peptide system gene variants are associated with ventricular dysfunction after coronary artery bypass grafting

Amanda A Fox et al. Anesthesiology. 2009 Apr.

Abstract

Background: Ventricular dysfunction (VnD) after primary coronary artery bypass grafting is associated with increased hospital stay and mortality. Natriuretic peptides have compensatory vasodilatory, natriuretic, and paracrine influences on myocardial failure and ischemia. The authors hypothesized that natriuretic peptide system gene variants independently predict risk of VnD after primary coronary artery bypass grafting.

Methods: A total of 1,164 patients undergoing primary coronary artery bypass grafting with cardiopulmonary bypass at two institutions were prospectively enrolled. After prospectively defined exclusions, 697 patients of European descent (76 with VnD) were analyzed. VnD was defined as need for at least 2 new inotropes and/or new mechanical ventricular support after coronary artery bypass grafting. A total of 139 haplotype-tagging single nucleotide polymorphisms (SNPs) within 7 genes (NPPA, NPPB, NPPC, NPR1, NPR2, NPR3, CORIN) were genotyped. SNPs univariately associated with VnD were entered into logistic regression models adjusting for clinical covariates predictive of VnD. To control for multiple comparisons, permutation analyses were conducted for all SNP associations.

Results: After adjusting for clinical covariates and multiple comparisons within each gene, seven NPPA/NPPB SNPs (rs632793, rs6668352, rs549596, rs198388, rs198389, rs6676300, rs1009592) were associated with decreased risk of postoperative VnD (additive model; odds ratios 0.44-0.55; P = 0.010- 0.036) and four NPR3 SNPs (rs700923, rs16890196, rs765199, rs700926) were associated with increased risk of postoperative VnD (recessive model; odds ratios 3.89-4.28; P = 0.007-0.034).

Conclusions: Genetic variation within the NPPA/NPPB and NPR3 genes is associated with risk of VnD after primary coronary artery bypass grafting. Knowledge of such genotypic predictors may result in better understanding of the molecular mechanisms underlying postoperative VnD.

PubMed Disclaimer

Figures

Figure 1

Figure 1

Block structure of linkage disequilibrium for the 28 successfully genotyped single nucleotide polymorphisms (SNPs) in the natriuretic peptide precursor protein A and B gene regions (NPPA/NPPB) on chromosome 1p36.22. SNPs surrounded by boxes are the SNPs that were significantly associated with the ventricular dysfunction phenotype after adjustment for clinical covariates and multiple comparisons (P<0.05). Stronger correlations between SNPs are noted by darker color in the intersecting squares linking each pair of SNPs. Stronger correlation indicates a tendency for the minor allele of one SNP to be inherited with the minor allele of the other SNP that it is being linked with in this figure. Correlations and block structures were estimated using Haploview (version 4.1; The Broad Institute, Cambridge, MA).

Figure 2

Figure 2

Block structure of linkage disequilibrium for the 32 successfully genotyped single nucleotide polymorphisms (SNPs) in the natriuretic peptide receptor C gene region (NPR3) on chromosome 5p13.3. SNPs surrounded by boxes are the SNPs that were significantly associated with the ventricular dysfunction phenotype after adjustment for clinical covariates and multiple comparisons (P<0.05). Stronger correlations between SNPs are noted by darker color in the intersecting squares linking each pair of SNPs. Stronger correlation indicates a tendency for the minor allele of one SNP to be inherited with the minor allele of the other SNP that it is being linked with in this figure. Correlations and block structures were estimated using Haploview (version 4.1; The Broad Institute, Cambridge, MA).

Comment in

Similar articles

Cited by

References

    1. Hutfless R, Kazanegra R, Madani M, Bhalla MA, Tulua-Tata A, Chen A, Clopton P, James C, Chiu A, Maisel AS. Utility of B-type natriuretic peptide in predicting postoperative complications and outcomes in patients undergoing heart surgery. J Am Coll Cardiol. 2004;43:1873–1879. - PubMed
    1. Fox AA, Shernan SK, Collard CD, Liu KY, Aranki SF, DeSantis SM, Jarolim P, Body SC. Preoperative B-type natriuretic peptide is as independent predictor of ventricular dysfunction and mortality after primary coronary artery bypass grafting. J Thorac Cardiovasc Surg. 2008;136:452–461. - PMC - PubMed
    1. Provenchere S, Berroeta C, Reynaud C, Baron G, Poirier I, Desmonts JM, Iung B, Dehoux M, Philip I, Benessiano J. Plasma brain natriuretic peptide and cardiac troponin I concentrations after adult cardiac surgery: association with postoperative cardiac dysfunction and 1-year mortality. Crit Care Med. 2006;34:995–1000. - PubMed
    1. Cea LB. Natriuretic peptide family: new aspects. Curr Med Chem Cardiovasc Hematol Agents. 2005;3:87–98. - PubMed
    1. Itoh H, Suga S, Ogawa Y, Komatsu Y, Tamura N, Igaki T, Yamashita J, Ikeda T, Doi K, Chun TH, Inoue M, Matsuda K, Yoshimasa T, Ueda M, Ban T, Nakao K. Significance of vascular natriuretic peptide system in vascular remodeling in humans and its application to gene therapy. Ann N Y Acad Sci. 1997;811:533–541. - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources