The ZPR1 genotype predicts myocardial infarction in patients with familial hypercholesterolemia

The rs964184 variant in the ZPR1 gene has been associated with blood lipids and cardiovascular disease risk in the general population through genome-wide association study, but its effect in patients with familial hypercholesterolemia (FH) has never been studied.

The objectives of the present study are to investigate the effect of the rs964184 SNP on blood lipids and on the risk of incident myocardial infarction (MI) in patients with FH.

This study included 725 patients with genetically confirmed FH. The MI events that occurred throughout the lifespan until the last medical visit were included. The median observation period was 50 years. An exome chip genotyping method (Illumina) was used to impute the rs964184 genotype.

Among the 725 patients, 190 individuals carried one risk allele G (CG genotype), whereas 15 patients were carriers of the GG genotype. A significant difference in circulating triglycerides was observed between the 3 groups (1.33 [1.03-1.73] vs 1.46 [1.09-2.11] vs 1.56 [1.07-2.42] mmol/L, for the CC, CG, and GG carriers, respectively, P = .004 for the analysis of variance). The ZPR1 SNP rs964184 was significantly associated with MI even after correction for classical cardiovascular risk factors (hazard ratio 5.68, 95% confidence interval 2.40-13.45, P = .00008).

The cardiovascular risk in patients with FH is highly heterogeneous, and this study suggests that the rs964184 variant of the ZPR1 gene represents one of the important modulating factors.