Corin gene minor allele defined by 2 missense mutations is common in blacks and associated with high blood pressure and hypertension

Daniel L. Dries, Ronald G. Victor, J. Eduardo Rame, Richard S. Cooper, Xiaodong Wu, Xiaofeng Zhu, David Leonard, Su Inn Ho, Qingyu Wu, Wendy Post, Mark H. Drazner

Research output: Contribution to journalArticle

153 Citations (Scopus)

Abstract

Background - The natriuretic peptide system contributes to blood pressure regulation. Atrial and brain natriuretic peptides are cleaved into smaller biologically active molecules by corin, a transmembrane serine protease expressed in cardiomyocytes. Method and Results - This genotype-phenotype genetic association study included replication samples and genomic control to correct for population stratification. Sequencing of the human corin gene identified 2 nonsynonymous, nonconservative single nucleotide polymorphisms (Q568P and T555I) in near-complete linkage disequilibrium, thus describing a single minor I555 (P568) corin gene allele. This allele was present in the heterozygote state in ≈12% of blacks but was extremely rare in whites (<0.5% were homozygous for the minor allele). In our primary population sample, the Dallas Heart Study, after adjustment for potential confounders, including population stratification, the corin I555 (P568) allele remained independently associated with increased risk for prevalent hypertension (odds ratio, 1.63; 95% CI, 1.11 to 2.38; P=0.013). The corin I555 (P568) allele also was associated with higher systolic blood pressure in subjects not using antihypertensive medication in unadjusted (133.7±20.7 versus 129.4±17.4 mmHg; P=0.029) and adjusted (132.5±1.6 versus 128.9±0.6 mm Hg; P=0.029) analyses. The independent association of the minor corin allele with increased risk for prevalent hypertension was confirmed in the Multi-Ethnic Study of Atherosclerosis (odds ratio, 1.50; 95% CI, 1.09 to 2.06; P=0.014). In addition, the association of the minor corin I555 (P568) allele with higher systolic blood pressure was confirmed in adjusted analysis in the Chicago Genetics of Hypertension Study (125.8±1.9 versus 121.4±0.7 mm Hg; P=0.03). Conclusions - The corin I555 (P568) allele is common in blacks and is associated with higher blood pressure and an increased risk for prevalent hypertension.

Original languageEnglish (US)
Pages (from-to)2403-2410
Number of pages8
JournalCirculation
Volume112
Issue number16
DOIs
StatePublished - Oct 18 2005

Fingerprint

Missense Mutation
Alleles
Hypertension
Genes
Genetic Association Studies
Blood Pressure
Odds Ratio
Population
Natriuretic Peptides
Brain Natriuretic Peptide
Linkage Disequilibrium
Atrial Natriuretic Factor
Serine Proteases
Heterozygote
Cardiac Myocytes
Antihypertensive Agents
Single Nucleotide Polymorphism
Atherosclerosis

Keywords

  • Atrial natriuretic factor
  • Genes
  • Genetics
  • Hypertension
  • Peptides

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Corin gene minor allele defined by 2 missense mutations is common in blacks and associated with high blood pressure and hypertension. / Dries, Daniel L.; Victor, Ronald G.; Rame, J. Eduardo; Cooper, Richard S.; Wu, Xiaodong; Zhu, Xiaofeng; Leonard, David; Ho, Su Inn; Wu, Qingyu; Post, Wendy; Drazner, Mark H.

In: Circulation, Vol. 112, No. 16, 18.10.2005, p. 2403-2410.

Research output: Contribution to journalArticle

Dries, DL, Victor, RG, Rame, JE, Cooper, RS, Wu, X, Zhu, X, Leonard, D, Ho, SI, Wu, Q, Post, W & Drazner, MH 2005, 'Corin gene minor allele defined by 2 missense mutations is common in blacks and associated with high blood pressure and hypertension', Circulation, vol. 112, no. 16, pp. 2403-2410. https://doi.org/10.1161/CIRCULATIONAHA.105.568881
Dries, Daniel L. ; Victor, Ronald G. ; Rame, J. Eduardo ; Cooper, Richard S. ; Wu, Xiaodong ; Zhu, Xiaofeng ; Leonard, David ; Ho, Su Inn ; Wu, Qingyu ; Post, Wendy ; Drazner, Mark H. / Corin gene minor allele defined by 2 missense mutations is common in blacks and associated with high blood pressure and hypertension. In: Circulation. 2005 ; Vol. 112, No. 16. pp. 2403-2410.
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abstract = "Background - The natriuretic peptide system contributes to blood pressure regulation. Atrial and brain natriuretic peptides are cleaved into smaller biologically active molecules by corin, a transmembrane serine protease expressed in cardiomyocytes. Method and Results - This genotype-phenotype genetic association study included replication samples and genomic control to correct for population stratification. Sequencing of the human corin gene identified 2 nonsynonymous, nonconservative single nucleotide polymorphisms (Q568P and T555I) in near-complete linkage disequilibrium, thus describing a single minor I555 (P568) corin gene allele. This allele was present in the heterozygote state in ≈12{\%} of blacks but was extremely rare in whites (<0.5{\%} were homozygous for the minor allele). In our primary population sample, the Dallas Heart Study, after adjustment for potential confounders, including population stratification, the corin I555 (P568) allele remained independently associated with increased risk for prevalent hypertension (odds ratio, 1.63; 95{\%} CI, 1.11 to 2.38; P=0.013). The corin I555 (P568) allele also was associated with higher systolic blood pressure in subjects not using antihypertensive medication in unadjusted (133.7±20.7 versus 129.4±17.4 mmHg; P=0.029) and adjusted (132.5±1.6 versus 128.9±0.6 mm Hg; P=0.029) analyses. The independent association of the minor corin allele with increased risk for prevalent hypertension was confirmed in the Multi-Ethnic Study of Atherosclerosis (odds ratio, 1.50; 95{\%} CI, 1.09 to 2.06; P=0.014). In addition, the association of the minor corin I555 (P568) allele with higher systolic blood pressure was confirmed in adjusted analysis in the Chicago Genetics of Hypertension Study (125.8±1.9 versus 121.4±0.7 mm Hg; P=0.03). Conclusions - The corin I555 (P568) allele is common in blacks and is associated with higher blood pressure and an increased risk for prevalent hypertension.",
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T1 - Corin gene minor allele defined by 2 missense mutations is common in blacks and associated with high blood pressure and hypertension

AU - Dries, Daniel L.

AU - Victor, Ronald G.

AU - Rame, J. Eduardo

AU - Cooper, Richard S.

AU - Wu, Xiaodong

AU - Zhu, Xiaofeng

AU - Leonard, David

AU - Ho, Su Inn

AU - Wu, Qingyu

AU - Post, Wendy

AU - Drazner, Mark H.

PY - 2005/10/18

Y1 - 2005/10/18

N2 - Background - The natriuretic peptide system contributes to blood pressure regulation. Atrial and brain natriuretic peptides are cleaved into smaller biologically active molecules by corin, a transmembrane serine protease expressed in cardiomyocytes. Method and Results - This genotype-phenotype genetic association study included replication samples and genomic control to correct for population stratification. Sequencing of the human corin gene identified 2 nonsynonymous, nonconservative single nucleotide polymorphisms (Q568P and T555I) in near-complete linkage disequilibrium, thus describing a single minor I555 (P568) corin gene allele. This allele was present in the heterozygote state in ≈12% of blacks but was extremely rare in whites (<0.5% were homozygous for the minor allele). In our primary population sample, the Dallas Heart Study, after adjustment for potential confounders, including population stratification, the corin I555 (P568) allele remained independently associated with increased risk for prevalent hypertension (odds ratio, 1.63; 95% CI, 1.11 to 2.38; P=0.013). The corin I555 (P568) allele also was associated with higher systolic blood pressure in subjects not using antihypertensive medication in unadjusted (133.7±20.7 versus 129.4±17.4 mmHg; P=0.029) and adjusted (132.5±1.6 versus 128.9±0.6 mm Hg; P=0.029) analyses. The independent association of the minor corin allele with increased risk for prevalent hypertension was confirmed in the Multi-Ethnic Study of Atherosclerosis (odds ratio, 1.50; 95% CI, 1.09 to 2.06; P=0.014). In addition, the association of the minor corin I555 (P568) allele with higher systolic blood pressure was confirmed in adjusted analysis in the Chicago Genetics of Hypertension Study (125.8±1.9 versus 121.4±0.7 mm Hg; P=0.03). Conclusions - The corin I555 (P568) allele is common in blacks and is associated with higher blood pressure and an increased risk for prevalent hypertension.

AB - Background - The natriuretic peptide system contributes to blood pressure regulation. Atrial and brain natriuretic peptides are cleaved into smaller biologically active molecules by corin, a transmembrane serine protease expressed in cardiomyocytes. Method and Results - This genotype-phenotype genetic association study included replication samples and genomic control to correct for population stratification. Sequencing of the human corin gene identified 2 nonsynonymous, nonconservative single nucleotide polymorphisms (Q568P and T555I) in near-complete linkage disequilibrium, thus describing a single minor I555 (P568) corin gene allele. This allele was present in the heterozygote state in ≈12% of blacks but was extremely rare in whites (<0.5% were homozygous for the minor allele). In our primary population sample, the Dallas Heart Study, after adjustment for potential confounders, including population stratification, the corin I555 (P568) allele remained independently associated with increased risk for prevalent hypertension (odds ratio, 1.63; 95% CI, 1.11 to 2.38; P=0.013). The corin I555 (P568) allele also was associated with higher systolic blood pressure in subjects not using antihypertensive medication in unadjusted (133.7±20.7 versus 129.4±17.4 mmHg; P=0.029) and adjusted (132.5±1.6 versus 128.9±0.6 mm Hg; P=0.029) analyses. The independent association of the minor corin allele with increased risk for prevalent hypertension was confirmed in the Multi-Ethnic Study of Atherosclerosis (odds ratio, 1.50; 95% CI, 1.09 to 2.06; P=0.014). In addition, the association of the minor corin I555 (P568) allele with higher systolic blood pressure was confirmed in adjusted analysis in the Chicago Genetics of Hypertension Study (125.8±1.9 versus 121.4±0.7 mm Hg; P=0.03). Conclusions - The corin I555 (P568) allele is common in blacks and is associated with higher blood pressure and an increased risk for prevalent hypertension.

KW - Atrial natriuretic factor

KW - Genes

KW - Genetics

KW - Hypertension

KW - Peptides

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