title: Cardiovascular diseases-relatedGNB3C825T polymorphism has a significant sex-specific effect on serum soluble E-selectin levels.
abstract: BACKGROUND
  The C825T polymorphism (rs5443) of the Guanine Nucleotide-Binding protein subunit β3 (GNB3) gene has been associated with obesity, essential hypertension, atherosclerosis, coronary diseases, and cerebrovascular events, but with some sex-specific effects. Its association with inflammatory mediators such as cell adhesion molecules has not been studied, although they are heavily involved in cardiovascular diseases' (CVDs) processes. The aim of our study was then to investigate a possible sex-specific effect of theGNB3C825T polymorphism on serum soluble cell adhesion molecules such as E, P and L-selectins (sE, sP and sL-selectins).
  
  
  RESULTS
  Participants were from the STANISLAS Family Study and were free of chronic disease as CVDs or cancer. We included in total 771 subjects aged 6 to 58 years (391 males (50.71%) and 380 females (49.29%)). No significant association of rs5443 was observed in the whole population with serum sE, sP and sL-selectins after adjusting for age, sex, body mass index, systolic blood pressure, anti-inflammatory drugs and hormonal drugs consumption. A significant interaction of rs5443 was observed with sex for sE-selectin (p< 0.001), but not for sP and sL-selectins. After adjusting for covariables, the T allele was significantly associated with an additive increase effect on serum sE-selectin levels in males (β = 5.03 ± 2.18;p= 0.020), while a significant additive decrease effect was observed in females (β =-4.46 ± 2.06;p= 0.030). These associations stayed significant after correction for multiple tests (p= 0.045 in males and in females). The additive phenotypic variance was 21.54% in males versus 1.91% in females.
  
  
  CONCLUSIONS
  In our Caucasian population, theGNB3C825T polymorphism showed a significant sex-specific effect on serum sE-selectin levels, with a disadvantage for males, as increased sE-selectin levels has been associated with CVDs outcomes. The T allele has been previously associated with the same CVDs as increased sE-selectin, but more often in males. The link we observed between this polymorphism and E-selectin is then consistent with previous findings, and helps to better understand the deleterious effect of theGNB3825 T allele on CVDs outcomes in males. We revealed in this study an important pathway through which theGNB3gene induces CVDs' outcomes.
authors.affiliation: UMR INSERM U1122; IGE-PCV "Interaction Gène-Environnement en Physiopathologie CardioVasculaire", Faculté de Pharmacie, Université de Lorraine, Nancy, F-54000 France.
authors.forename: Kokoè Mélinda
authors.initials: KM
authors.lastname: Gbadoe
authors.affiliation: UMR INSERM U1122; IGE-PCV "Interaction Gène-Environnement en Physiopathologie CardioVasculaire", Faculté de Pharmacie, Université de Lorraine, Nancy, F-54000 France.
authors.forename: Nazha
authors.initials: N
authors.lastname: Berdouzi
authors.affiliation: UMR INSERM U1122; IGE-PCV "Interaction Gène-Environnement en Physiopathologie CardioVasculaire", Faculté de Pharmacie, Université de Lorraine, Nancy, F-54000 France.
authors.forename: Alex-Ander Aldasoro
authors.initials: AA
authors.lastname: Aguiñano
authors.affiliation: UMR INSERM U1122; IGE-PCV "Interaction Gène-Environnement en Physiopathologie CardioVasculaire", Faculté de Pharmacie, Université de Lorraine, Nancy, F-54000 France.
authors.forename: Ndeye Coumba
authors.initials: NC
authors.lastname: Ndiaye
authors.affiliation: UMR INSERM U1122; IGE-PCV "Interaction Gène-Environnement en Physiopathologie CardioVasculaire", Faculté de Pharmacie, Université de Lorraine, Nancy, F-54000 France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Visvikis-Siest
keywords: Cardiovascular diseases; Cell adhesion molecules; GNB3 gene; Selectins; Sex-specific effect