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Highly significant association between two common single nucleotide polymorphisms in CORIN gene and preeclampsia in Caucasian women.

Stepanian A, Alcaïs A, de Prost D, Tsatsaris V, Dreyfus M, Treluyer JM, Mandelbrot L, ECLAXIR Study Gro - PLoS ONE (2014)

Bottom Line: 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).Our findings further support the probability of a critical role of corin in preeclamspia pathophysiology at the uteroplacental interface.

View Article: PubMed Central - PubMed

Affiliation: Service d'Hématologie Biologique, Hôpital Lariboisière, Paris, France.

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.

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Flow chart for the enrollment of the study population and the SNP analysis.
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pone-0113176-g001: Flow chart for the enrollment of the study population and the SNP analysis.

Mentions: We included 639 patients. Seven controls who developed PE after enrollment, 26 patients with unmatchable mixed ethnic origins and 35 patients with insufficient amounts of DNA for genotyping were excluded from the analysis. In the current study, we analyzed 571 matched subjects (295 cases and 276 controls) (Figure 1).


Highly significant association between two common single nucleotide polymorphisms in CORIN gene and preeclampsia in Caucasian women.

Stepanian A, Alcaïs A, de Prost D, Tsatsaris V, Dreyfus M, Treluyer JM, Mandelbrot L, ECLAXIR Study Gro - PLoS ONE (2014)

Flow chart for the enrollment of the study population and the SNP analysis.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4256174&req=5

pone-0113176-g001: Flow chart for the enrollment of the study population and the SNP analysis.
Mentions: We included 639 patients. Seven controls who developed PE after enrollment, 26 patients with unmatchable mixed ethnic origins and 35 patients with insufficient amounts of DNA for genotyping were excluded from the analysis. In the current study, we analyzed 571 matched subjects (295 cases and 276 controls) (Figure 1).

Bottom Line: 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).Our findings further support the probability of a critical role of corin in preeclamspia pathophysiology at the uteroplacental interface.

View Article: PubMed Central - PubMed

Affiliation: Service d'Hématologie Biologique, Hôpital Lariboisière, Paris, France.

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.

Show MeSH
Related in: MedlinePlus