title: Corin gene minor allele defined by 2 missense mutations is common in blacks and associated with high blood pressure and hypertension.
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.
  
  
  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 mm Hg; 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.
authors.affiliation: Donald W. Reynolds Cardiovascular Clinical Research Center, Division of Cardiology, University of Texas at Southwestern Medical Center, Dallas, USA. daniel.dries@uphs.upenn.edu
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Dries
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Victor
authors.forename: J Eduardo
authors.initials: JE
authors.lastname: Rame
authors.forename: Richard S
authors.initials: RS
authors.lastname: Cooper
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Wu
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Zhu
authors.forename: David
authors.initials: D
authors.lastname: Leonard
authors.forename: Su-Inn
authors.initials: SI
authors.lastname: Ho
authors.forename: Qingyu
authors.initials: Q
authors.lastname: Wu
authors.forename: Wendy
authors.initials: W
authors.lastname: Post
authors.forename: Mark H
authors.initials: MH
authors.lastname: Drazner
mesh_terms: D000328:Adult; D000368:Aged; D044383:Black People / Q000235:genetics*; D001794:Blood Pressure; D003331:Coronary Vessels / Q000502:physiology / Q000503:physiopathology; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000235:genetics*; D008875:Middle Aged; D020125:Mutation, Missense; D010641:Phenotype; D015995:Prevalence; D012697:Serine Endopeptidases / Q000235:genetics*; D013781:Texas; D001741:Black or African American
chemical_list: C119812:CORIN protein, human; D012697:Serine Endopeptidases