PHACTR1 genotype predicts coronary artery disease in patients with familial hypercholesterolemia

Familial hypercholesterolemia (FH) is the most frequent autosomal codominant disease worldwide and is characterized by elevated low-density lipoprotein cholesterol and premature coronary artery disease (CAD). Polymorphisms in phosphatase and actin regulator 1 (PHACTR1) have been shown to be associated with cardiovascular risk in large genome-wide association studies studies.

The aim of the present study is to evaluate the association between the rs12526453 polymorphism in the PHACTR1 gene and the prevalence of CAD in FH patients.

A cohort of 668 adult genetically confirmed heterozygous FH subjects were included in the present study. Logistic regression models were used to evaluate the strength of the association between rs12526453 genotype and CAD prevalence.

Noncarriers (CC) of the rs12526453 represented 41% of the cohort, whereas heterozygous (CG) and homozygous (GG) carriers represented 44% and 15%, respectively. The prevalence of CAD was significantly higher in non-carriers of the rs12526453 polymorphism compared to heterozygous and homozygous carriers (38.0%, 25.8%, 24.5%, respectively, P = .001). When a dominant logistic regression model was studied, the association between this single-nucleotide polymorphism and CAD prevalence was significant even after correction for all classical cardiovascular risk factors (odds ratio 0.48, 95% confidence intervals 0.31-0.74, P = .001).

In the present study, we have shown that the rs12526453 single-nucleotide polymorphism of the PHACTR1 gene is significantly associated with a 50% reduction in the odds of CAD events in FH subjects. Because the protective G allele is frequent in the Caucasian population (allelic frequency of 0.26), screening for this polymorphism in Caucasian FH subjects could further help to stratify risk of CAD in this population.