Association of the C-Reactive Protein Gene (CRP) rs1205 C>T Polymorphism with Aortic Valve Calcification in Patients with Aortic Stenosis.

Ewa Wypasek,Daniel Potaczek,Anetta Undas

doi:10.3390/ijms161023745

Abstract

Elevation in C-reactive protein (CRP) levels have been shown in patients with aortic valve stenosis (AS). Minor allele of the CRP gene (CRP) rs1205 C>T polymorphism has been associated with lower plasma CRP concentrations in cohorts of healthy and atherosclerotic patients. Considering the existing similarities between atherosclerosis and AS, we examined the effect of CRP rs1205 C>T polymorphism on the AS severity. Three hundred consecutive Caucasian patients diagnosed with AS were genotyped for the rs1205 C>T polymorphism using the TaqMan assay. Severity of the AS was assessed using transthoracic echocardiography. The degree of calcification was analyzed semi-quantitatively. Carriers of the rs1205 T allele were characterized by elevated serum CRP levels (2.53 (1.51–3.96) vs. 1.68 (0.98–2.90) mg/L, p < 0.001) and a higher proportion of the severe aortic valve calcification (70.4% vs. 55.1%, p = 0.01) compared with major homozygotes. The effect of CRP rs1205 polymorphism on CRP levels is opposite in AS-affected than in unaffected subjects, suggesting existence of a disease-specific molecular regulatory mechanism. Furthermore, rs1205 variant allele predisposes to larger aortic valve calcification, potentially being a novel genetic risk marker of disease progression.

Highlights

Aortic stenosis (AS) is currently the most commonly acquired valvular heart disease in developed countries
The T allele frequency of 38.3% was not much higher than in the previous Caucasian population- or healthy subjects-based studies on the rs1205 polymorphisms, in which it reached a value of 32.5% [13], 34.4% [20] or 34.2% [15]
The rs1205 polymorphism minor allele frequency of 34.5% was completely in line with those reached in community- or healthy individuals-based studies conducted in subjects of European descent and given above [13,14,15]

Summary

Introduction

Aortic stenosis (AS) is currently the most commonly acquired valvular heart disease in developed countries. C-reactive protein (CRP) is a biomarker of inflammation with predictive value for cardiac events in both, apparently healthy subjects and patients with coronary artery disease (CAD), a cardiac manifestation of atherosclerosis [6]. Several studies [7,8,9], not all [10,11], found an association between plasma CRP levels and severity and/or progression of AS. Elevated CRP levels have been reported in patients with severe symptomatic AS awaiting valve surgery [9] which were declining after aortic valve replacement [7]. A rapid increase in AS severity has been associated with elevated CRP levels, suggesting that CRP may be a marker of AS progression [12]

Methods

Results

Conclusion