INSERM UMR U1122, IGE-PCV 'Interactions Gène-Environnement en Physiopathologie Cardio-vasculaire', Faculté de Pharmacie - Université de Lorraine, Nancy, France.
Department of Internal Medicine and Geriatrics, CHU Technopôle Nancy-Brabois, Vandoeuvre-lès-Nancy, France.
Clin Chem Lab Med. 2018 Apr 25;56(5):748-754. doi: 10.1515/cclm-2017-0347.
The ABO gene has been widely studied and associated with many different diseases such as myocardial infarction and diabetes. Pleiotropic effects of the ABO locus have been demonstrated. Indeed it affects different phenotypes such as E- and P-selectins, triglycerides and total cholesterol. The goal of this work was to study the SNP rs644234 located in the ABO gene with different phenotypes related with diseases where the ABO gene has been involved.
We analyzed the SNP rs644234 located in the ABO gene, by performing association studies with different lipid phenotypes as well as with the soluble E-selectin levels in 348 adults from the STANISLAS Family Study.
The major rs644234T allele was associated with increased levels of soluble E-selectin (p=8.7×10-12). According to the lipid phenotypes, the major rs644234T allele was associated with decreased levels of apolipoproteins E (ApoE) (p=0.001) and low-density lipoprotein cholesterol (LDL-C) (p=0.032) but was associated with increased levels of high-density lipoprotein cholesterol (HDL-C) (p=0.013). The association of the HDL-C was especially significant in the male individuals (p=0.001).
We confirmed that ABO is a major locus for serum soluble E-selectin levels variability, and we also correlated this gene with different lipid phenotypes. Furthermore, we demonstrated that this pleiotropic effect is independent. This is the first time that a correlation has been made between the ABO gene and the ApoE levels. According to these results, the major allele of this polymorphism may have a protective effect when it comes to cardiovascular related diseases, and more specifically when it comes to the lipid phenotypes.
ABO 基因已被广泛研究，并与许多不同的疾病相关，如心肌梗死和糖尿病。ABO 基因座的多效性已得到证实。事实上，它会影响到不同的表型，如 E-和 P-选择素、甘油三酯和总胆固醇。本研究的目的是研究位于 ABO 基因中的 SNP rs644234，该基因与 ABO 基因参与的疾病相关的不同表型有关。
我们通过对 348 名来自 STANISLAS 家族研究的成年人进行不同脂质表型以及可溶性 E-选择素水平的关联研究，分析了位于 ABO 基因中的 SNP rs644234。
主要 rs644234T 等位基因与可溶性 E-选择素水平升高相关（p=8.7×10-12）。根据脂质表型，主要 rs644234T 等位基因与载脂蛋白 E（ApoE）水平降低（p=0.001）和低密度脂蛋白胆固醇（LDL-C）水平降低（p=0.032）相关，但与高密度脂蛋白胆固醇（HDL-C）水平升高相关（p=0.013）。这种与 HDL-C 的关联在男性中尤为显著（p=0.001）。
我们证实 ABO 是血清可溶性 E-选择素水平变异性的主要基因座，我们还将该基因与不同的脂质表型相关联。此外，我们证明这种多效性是独立的。这是首次将 ABO 基因与 ApoE 水平相关联。根据这些结果，这种多态性的主要等位基因可能对心血管相关疾病具有保护作用，特别是在脂质表型方面。
