title: Highly significant association between two common single nucleotide polymorphisms in CORIN gene and preeclampsia in Caucasian women.
abstract: Preeclampsia is a frequent medical complication during pregnancy. Corin, a serine protease which activates pro-atrial natriuretic peptide, has recently been shown to be involved in the pathophysiology of preeclampsia. The aim of this study was to search for CORIN gene variations and their association to preeclampsia in Caucasian and African women. Our study population was composed of 571 pregnant women (295 with preeclampsia and 276 normotensive controls) matched for maternal and gestational age, and ethnic origin. The 22 exons of the CORIN gene were sequenced in a discovery sample (n = 260), where 31 single nucleotide polymorphisms were identified. In a replication sample (n = 311), 4 single nucleotide polymorphisms were tested. Two minor alleles (C for rs2271036 and G for rs2271037) were significantly associated to preeclampsia. Adjusted odds ratios [95% confidence interval] were 2.5 [1.2-3.8] (p = 0.007) and 2.3 [1.5-3.5] (p = 1.3 × 10(-4)), respectively. These associations were ethnic-specific, as only found in the Caucasian of subjects (odds ratio = 3.5 [1.8-6.6], p = 1.1 × 10(-4); odds ratio = 3.1 [1.7-5.8], p = 2.1 × 10(-4), for each single nucleotide polymorphism, respectively). The two single nucleotide polymorphisms are in almost perfect linkage disequilibrium (r(2) = 0.93). No specific association was found with severe preeclampsia, early-onset preeclampsia nor fetal growth retardation. In conclusion, this is the first report of a highly significant association between these two single nucleotide polymorphisms in CORIN gene and preeclampsia. Our findings further support the probability of a critical role of corin in preeclamspia pathophysiology at the uteroplacental interface.
authors.affiliation: Service d'Hématologie Biologique, Hôpital Lariboisière, Paris, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Stepanian
authors.affiliation: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale, U1163, Imagine Institute, Paris, France; University Paris Descartes, Sorbonne Paris Cité, Paris, France; St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, New York, United States of America; INSERM CIC P0901, Paris, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Alcaïs
authors.affiliation: Service d'Hématologie biologique et Transfusion, Hôpital Louis Mourier (AP-HP), Colombes, France; Unité 770, INSERM, Le Kremlin-Bicêtre, France; Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: de Prost
authors.affiliation: Service de Gynécologie-Obstétrique, Hôpital Port-Royal (AP-HP), Paris, France; Unité 767, INSERM, Université Paris Descartes, Paris, France; Département Hospitalo-Universitaire Risque et Grossesse, Paris, France; Fondation PremUP, Paris, France.
authors.forename: Vassilis
authors.initials: V
authors.lastname: Tsatsaris
authors.affiliation: CHU Clémenceau, Unité de Gynécologie-Obstétrique et Médecine de la Reproduction, Caen, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Dreyfus
authors.affiliation: University Paris Descartes, Sorbonne Paris Cité, Paris, France; Département Hospitalo-Universitaire Risque et Grossesse, Paris, France; INSERM CIC P0901, Paris, France.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Treluyer
authors.affiliation: Département Hospitalo-Universitaire Risque et Grossesse, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, Paris, France; AP-HP, Hôpital Louis Mourier, service de Gynécologie-Obstétrique, Colombes, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Mandelbrot
mesh_terms: D000328:Adult; D000483:Alleles; D044383:Black People; D001794:Blood Pressure / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011225:Pre-Eclampsia / Q000235:genetics* / Q000473:pathology; D011247:Pregnancy; D012697:Serine Endopeptidases / Q000235:genetics*; D044465:White People
chemical_list: C119812:CORIN protein, human; D012697:Serine Endopeptidases