Gbadoe Kokoè Mélinda, Berdouzi Nazha, Aguiñano Alex-Ander Aldasoro, Ndiaye Ndeye Coumba, Visvikis-Siest Sophie
UMR INSERM U1122; IGE-PCV "Interaction Gène-Environnement en Physiopathologie CardioVasculaire", Faculté de Pharmacie, Université de Lorraine, Nancy, F-54000 France.
J Inflamm (Lond). 2016 Dec 9;13:39. doi: 10.1186/s12950-016-0146-z. eCollection 2016.
The C825T polymorphism (rs5443) of the Guanine Nucleotide-Binding protein subunit β3 () 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 the C825T polymorphism on serum soluble cell adhesion molecules such as E, P and L-selectins (sE, sP and sL-selectins).
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 ( < 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; = 0.020), while a significant additive decrease effect was observed in females (β =-4.46 ± 2.06; = 0.030). These associations stayed significant after correction for multiple tests ( = 0.045 in males and in females). The additive phenotypic variance was 21.54% in males versus 1.91% in females.
In our Caucasian population, the C825T 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 the 825 T allele on CVDs outcomes in males. We revealed in this study an important pathway through which the gene induces CVDs' outcomes.
鸟嘌呤核苷酸结合蛋白β3（GNB3）基因的C825T多态性（rs5443）与肥胖、原发性高血压、动脉粥样硬化、冠心病和脑血管事件有关，但存在一些性别特异性影响。尽管细胞黏附分子等炎症介质在心血管疾病（CVD）过程中起重要作用，但其与该多态性的关联尚未得到研究。因此，我们研究的目的是调查GNB3基因C825T多态性对血清可溶性细胞黏附分子如E、P和L-选择素（sE、sP和sL-选择素）可能存在的性别特异性影响。
参与者来自斯坦尼斯拉斯家族研究，且无CVD或癌症等慢性疾病。我们共纳入了771名年龄在6至58岁的受试者（391名男性（50.71%）和380名女性（49.29%））。在调整年龄、性别、体重指数、收缩压、抗炎药物和激素药物使用情况后，未观察到rs5443与全人群血清sE、sP和sL-选择素之间存在显著关联。观察到rs5443与sE-选择素的性别存在显著交互作用（P<0.001），但与sP和sL-选择素不存在交互作用。在调整协变量后，T等位基因与男性血清sE-选择素水平的加性增加效应显著相关（β=5.03±2.18；P=0.020），而在女性中观察到显著的加性降低效应（β=-4.46±2.06；P=0.030）。在进行多重检验校正后，这些关联仍然显著（男性和女性的P值均为0.
