Journal Article

Association between lipoprotein(a) (Lp(a)) levels and Lp(a) genetic variants with coronary artery calcification

Moebus, Susanne, Mahabadi, Amir A., Hoffmann, Per, Erbel, Raimund, Pechlivanis, Sonali, Broecker-Preuss, Martina, Nöthen, Markus M., Stang, Andreas, Jöckel, Karl-Heinz

2020

Overview

Background To examine the association between lipoprotein(a) (Lp(a)) levels, LPA (rs10455872 and rs3798220) and IL1F9 (rs13415097) single nucleotide polymorphisms (SNPs) with coronary artery calcification (CAC), an important predictor for coronary artery disease (CAD). Methods We used data from 3799 (mean age ± SD: 59.0 ± 7.7 years, 47.1% men) Heinz Nixdorf Recall study participants. We applied linear regression models to explore the relation between the log-transformed Lp(a) levels and LPA and IL1F9 SNPs with log e (CAC + 1). The association between the SNPs and log-transformed Lp(a) levels was further assessed using linear regression. The models were adjusted for age and sex (Model 1) and additionally for Lp(a) levels (Model 2). Results We observed a statistically significant association between log-transformed Lp(a) levels and CAC (Model 1: beta per log-unit increase in Lp(a) levels = 0.11; 95% confidence interval [95% CI] [0.04; 0.18], p =  0.002). Furthermore, the LPA SNP rs10455872 showed a statistically significant association with CAC (Model 1: beta per allele = 0.37 [0.14; 0.61], p =  0.002). The association between rs10455872 and CAC was attenuated after adjustment for Lp(a) levels (Model 2: beta per allele = 0.26 [− 0.01; 0.53], p =  0.06). Both LPA SNPs also showed a statistically significant association with Lp(a) levels (Model 1: beta rs10455872 per allele: 1.56 [1.46; 1.65], p <  0.0001 and beta rs3798220 per allele: 1.51 [1.33; 1.69], p <  0.0001)). The Mendelian randomization analysis showed that Lp(a) is a causal risk factor for CAC (estimate per log-unit increase in Lp(a) levels (95% CI), p : 0.27 [0.11; 0.44], p =  0.001). The IL1F9 SNP did not show any statistically significant association with Lp(a) levels or with CAC. Conclusions We provide evidence for the association of LPA rs10455872 with higher levels of Lp(a) and CAC in our study. The results of our study suggest that rs10455872, mediated by Lp(a) levels, might play a role in promoting the development of atherosclerosis leading to cardiovascular disease events.

• Publisher: BioMed Central,BMC
• Subject: Age / Aged / Alleles / Arteriosclerosis / Atherosclerosis - blood / Atherosclerosis - epidemiology / Atherosclerosis - genetics / Biomedical and Life Sciences / Biomedicine / Blood pressure / Calcification / Calcification (ectopic) / Cardiovascular disease / Cardiovascular diseases / Cholesterol / Coronary artery / Coronary artery calcification / Coronary Artery Disease - blood / Coronary Artery Disease - epidemiology / Coronary Artery Disease - genetics / Coronary vessels / Coronary Vessels - pathology / Cytogenetics / Diabetes / Female / Gene Frequency / Gene Function / Genetic diversity / Genetic epidemiology and genetic associations / Genetic Predisposition to Disease / Genome-Wide Association Study / Genotype / Germany - epidemiology / Heart diseases / Human Genetics / Humans / Interleukin 1 / Lipids / Lipoprotein(a) - blood / Lipoprotein(a) - genetics / Low density lipoprotein / Lp(a) / LPA genetic variants / Male / Middle Aged / Polymorphism, Single Nucleotide / Regression analysis / Research Article / Risk Factors / Single-nucleotide polymorphism / Statistical analysis / Stroke / Studies / Vascular Calcification - blood / Vascular Calcification - epidemiology / Vascular Calcification - genetics