Abstract
Polymorphisms in the LPA gene have been associated with aortic valve calcification (AVC). There are wide differences in the allelic frequencies, Lp(a) levels, and the association with AVC among ethnic groups. The aim of this study was to determine the association of the LPA gene polymorphisms with Lp(a) levels and risk of developing AVC, in Mexican-Mestizos population. Six LPA polymorphisms (rs10455872, rs7765803, rs6907156, rs1321195, rs12212807 and rs6919346) were genotyped by TaqMan assays in 1,265 individuals without premature coronary artery disease. The presence of AVC was determined by computed tomography. The association of the LPA polymorphisms with AVC, Lp(a), and other cardiovascular risk factors (CVRF) was evaluated using logistic regression analysis. Compared to AA genotype, subjects with AG+GG genotypes had high prevalence of Lp(a) ≥ 30 mg/dL (7.1% vs. 23.7%, p<0.001) and AVC (19.0% vs. 29.4%, p=0.007). In a model adjusted for several CVRF, the LPA rs10455872-G allele was associated with high Lp(a) levels and AVC. Carriers of G allele had a high risk of Lp(a) ≥ 30 mg/dL (OR= 3.86, CI 95%: 2.2 - 6.7, p=0.001) and AVC (OR= 2.54, CI 95%: 1.56 - 4.14, p=0.001), independently of other CVRF. In this population, carriers of rs10455872-G allele had 3.86 and 2.54 higher risk of Lp(a) ≥ 30 mg/dL or presence of AVC, respectively.
Highlights
Lipoprotein(a) [Lp(a)] is a low density lipoprotein (LDL) bound to apo(a), a polymorphic glycoprotein of high molecular weight (300 to 800 kDa) very similar to plasminogen (McLean et al, 1987; Guevara et al, 1992)
We identified the coronary artery disease (CAD)-risk allele or the minor allele frequency (MAF); subjects carrying the risk allele were compared to homozygotes carrying the wild-type allele
The rs10455872-G polymorphism was associated with Aortic valve calcification (AVC) > 0 Hounsfield units (HU) (p=0.013)
Summary
Lipoprotein(a) [Lp(a)] is a low density lipoprotein (LDL) bound to apo(a), a polymorphic glycoprotein of high molecular weight (300 to 800 kDa) very similar to plasminogen (McLean et al, 1987; Guevara et al, 1992). A high concentration of Lp(a) is a documented risk factor for coronary artery disease (CAD) (Danesh et al, 2000; Nordestgaard et al, 2010). Aortic valve calcification (AVC) constitutes one of the first stages of valvular disease that can obstruct blood flow (Kamstrup et al, 2014). This condition has been found in 2% to 7% of the population older than 65 years of age (Aronow et al, 1999), and can reach 40% in individuals with other atherosclerosis risk factors, like smoking, diabetes, hypertension, and dyslipidemia (Taylor et al, 2005). AVC is an early marker of valvular disease and coronary atherosclerosis as it is associated with a 50% increase in the risk of myocardial infarction and cardiovascular mortality (Otto et al, 1999)
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