The Ser290Asn and Thr715Pro Polymorphisms of the SELP Gene Are Associated with A Lower Risk of Developing Acute Coronary Syndrome and Low Soluble P-Selectin Levels in A Mexican Population ‡.

Gabriel Herrera-Maya,Felipe Masso,Andros Vázquez-Montero,Oscar Pérez-Méndez,Galileo Escobedo,Gilberto Vargas-Alarcón,Teresa Juárez-Cedillo,Rosalinda Posadas-Sánchez,José Manuel Fragoso

doi:10.3390/biom10020270

Abstract

Recent studies have shown that P-selectin promotes the early formation of atherosclerotic plaque. The aim of the present study was to evaluate whether the SELP gene single nucleotide polymorphisms (SNPs) are associated with presence of acute coronary syndrome (ACS) and with plasma P-selectin levels in a case-control association study. The sample size was estimated for a statistical power of 80%. We genotyped three SELP (SELP Ser290Asn, SELP Leu599Val, and SELP Thr715Pro) SNPs using 5’ exonuclease TaqMan assays in 625 patients with ACS and 700 healthy controls. The associations were evaluated with logistic regressions under the co-dominant, dominant, recessive, over-dominant and additive inheritance models. The genotype contribution to the plasma P-selectin levels was evaluated by a Student’s t-test. Under different models, the SELP Ser290Asn (OR = 0.59, pCCo-Dominant = 0.047; OR = 0.59, pCDominant = 0.014; OR = 0.58, pCOver-Dominant = 0.061, and OR = 0.62, pCAdditive = 0.015) and SELP Thr715Pro (OR = 0.61, pCDominant = 0.028; OR = 0.63, pCOver-Dominant = 0.044, and OR = 0.62, pCAdditive = 0.023) SNPs were associated with a lower risk of ACS. In addition, these SNPs were associated with low plasma P-selectin levels. In summary, this study established that the SELP Ser290Asn and SELP Thr715Pro SNPs are associated with a lower risk of developing ACS and with decreased P-selectin levels in plasma in a Mexican population.

Highlights

Acute coronary syndrome (ACS) comprises a spectrum of obstructive coronary artery diseases that most commonly arise from plaque rupture and/or erosion, leaving the vulnerable lipid-rich core exposed to the circulation
Reiner et al reported in the CARDIA study that the SELP Ser290Asn and SELP Thr715Pro single nucleotide polymorphisms (SNPs) are associated with carotid intima-media thickness in young adults; these associations are different in European-American and African-American individuals [9]
In line with these data, Nasibullin et al reported that the 290Ans allele of the SELP Ser290Asn SNP is associated with a lower risk of MI in a Russian population [13]

Summary

Introduction

Acute coronary syndrome (ACS) comprises a spectrum of obstructive coronary artery diseases that most commonly arise from plaque rupture and/or erosion, leaving the vulnerable lipid-rich core exposed to the circulation. Platelets and the coagulation cascade are activated, leading to acute thrombotic occlusion [1,2]. This syndrome is a consequence of atherosclerosis associated with a strong inflammatory component, which is immune mediated by chemokines. These molecules have an important role in the development of atherosclerotic plaque [3,4,5]. Experimental studies have shown that higher expression of SELP increases adhesion, monocytes rolling to the vascular wall, accumulation of oxidized low-density lipoproteins, and the early formation of atherosclerotic plaque and other inflammatory diseases [4,5,6,7]

Objectives

Methods

Results

Conclusion