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 (r2 = 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.
Highlights
Preeclampsia (PE) is a frequent medical complication during pregnancy, occurring in 2% to 7% of pregnancies worldwide [1, 2]
There is evidence suggesting that these two sub-groups of PE might result from different mechanisms, with placental pathology being predominant in early-onset PE and maternal inflammatory state being predominant in late-onset PE [4, 7]
We report for the first time a highly significant association between two Single Nulceotide Polymorphiss (SNPs) located in the CORIN gene and PE in a large sample of 571 matched patients
Summary
Preeclampsia (PE) is a frequent medical complication during pregnancy, occurring in 2% to 7% of pregnancies worldwide [1, 2] It is an important cause of perinatal and maternal mortality and morbidity, in particular preterm birth. The earliest known abnormality is defective trophoblast invasion of the placenta, which disrupts uterine artery morphology and leads to placental hypoxia and ischemia. This is accompanied by the secretion by the syncytiotrophoblast of several soluble mediators into maternal circulation, some of which promote inflammation and result in maternal endothelial cell injury [4,5,6]. There is evidence suggesting that these two sub-groups of PE might result from different mechanisms, with placental pathology being predominant in early-onset PE and maternal inflammatory state being predominant in late-onset PE [4, 7]
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