VEGFR2 and OPG genes modify the risk of subclinical coronary atherosclerosis in patients with familial hypercholesterolemia.
BACKGROUND AND AIMS
Heterozygous familial hypercholesterolemia (FH) is a genetic disorder characterized by high levels of low-density lipoprotein cholesterol (LDL-C). The magnitude of atherosclerotic cardiovascular disease (ASCVD) risk in FH patients is highly variable, and this can result from genetic factors. The aim of our study was to characterize whether polymorphisms in VEGFR2 and OPG genes could influence the expression of ASCVD in FH patients.


METHODS
We studied 318 FH patients from the SAFEHEART registry, without clinical diagnosis of ASCVD. A coronary tomographic angiography (CTA) was performed to determine and evaluate the presence of coronary stenosis and coronary artery calcium, as measured by coronary calcium score (CCS). Genotyping of OPG rs2073618 and VEGFR2 rs2071559 polymorphisms was performed using TaqMan 5'-exonuclease allelic discrimination assays.


RESULTS
Homozygous GG genotype and G allele of VEGFR2 rs2071559 polymorphism were associated with decreased risk of developing coronary artery stenosis. In the analysis of OPG rs2073618 and VEGFR2 rs2071559 polymorphisms, according to the presence of coronary artery calcium, we found significant differences in both polymorphisms. Homozygous GG genotype and G allele of VEGFR2 rs2071559 polymorphism were associated with decreased risk of accumulation of coronary artery calcium measured by CCS in CTA. Moreover, being a carrier of the GG genotype and G allele of the OPG rs2073618 polymorphism increased the risk of the presence of coronary artery calcium measured by CCS in CTA.


CONCLUSIONS
Polymorphisms in VEGFR2 and OPG genes modify the risk of ASCVD in FH patients.
['Miramontes-González|José Pablo|JP|', 'Usategui-Martín|Ricardo|R|', 'Pérez de Isla|Leopoldo|L|', 'Alonso|Rodrigo|R|', 'Muñiz-Grijalvo|Ovidio|O|', 'Díaz-Díaz|José Luis|JL|', 'Zambón|Daniel|D|', 'Jiménez|Francisco Fuentes|FF|', 'Martín-Vallejo|Javier|J|', 'Rodríguez Gude|Ana Elisa|AE|', 'Jiménez|David León|DL|', 'Padro|Teresa|T|', 'González-Sarmiento|Rogelio|R|', 'Mata|Pedro|P|']
D000328:Adult D003324:Coronary Artery Disease D005260:Female D005838:Genotype D006720:Homozygote D006801:Humans D006938:Hyperlipoproteinemia Type II D008297:Male D008875:Middle Aged D053244:Osteoprotegerin D011110:Polymorphism, Genetic D011446:Prospective Studies D018570:Risk Assessment D040301:Vascular Endothelial Growth Factor Receptor-2
VEGFR2 OPG Familial hypercholesterolemia Polymorphism SAFEHEART Coronary calcium and coronary stenosis