SR-BI P376L Variant Linked to Dysfunctional HDL and Increased Cardiovascular Risk
In a cohort of 615 individuals followed for 7 years, carriers of the rare SCARB1 P376L variant had a 3.75-fold increased odds of cardiovascular disease and 13% higher HDL lipid peroxidation, despite normal HDL-cholesterol levels. Genotyping by TaqMan real-time PCR revealed that this variant produces dysfunctional HDL, suggesting that HDL quality, not just quantity, matters for cardiovascular risk assessment.
The original study
Rare P376L variant in the SR-BI gene associates with HDL dysfunction and risk of cardiovascular disease.
- Authors
- Samadi S, Farjami Z, Hosseini ZS, Ferns GA, Mohammadpour AH, Tayefi M, et al.
- Journal
- Clinical biochemistry
- Type
- Clinical Trial, Journal Article
- PMID
- 31251897
Original abstract
BACKGROUND: Scavenger receptor class B type 1 (SR-BI) encoded by SCARB1 gene serves as a multifunctional HDL receptor, facilitating the uptake of cholesteryl esters from HDL to the liver. Recent studies have identified the association between the P376L missense mutation of the SCARB1 gene with increased serum HDL-Cholesterol level. However, the contribution of this variant to the development of cardiovascular disease (CVD) remains unclear. OBJECTIVE: We have investigated the association between the P376L polymorphism with the properties of HDL and CVD outcomes in a population sample recruited as part of the Mashhad-Stroke and Heart-Atherosclerotic-Disorders (MASHAD) cohort. METHODS: Six hundred and fifteen individuals who had a median follow-up period of 7 years were recruited as part of the MASHAD cohort. Anthropometric, biochemical parameters and HDL lipid peroxidation (HDLox) were assessed. Genotyping was performed using TaqMan-real-time-PCR based method. The association of P376L-rs74830766 with cardiovascular-risk-factors and CVD events were evaluated. RESULTS: Carriers of the P376L variant were significantly more likely than non-carriers to develop CVD using multivariate analyses adjusted for traditional CVD risk factors defined as: age, sex, BMI, presence of diabetes, or hypertension, positive smoking habit, and total cholesterol (OR: 3.75, 95%CI: 1.76-7.98, p = 0.001). In an adjusted model, there was a two fold increase in cardiovascular endpoints among individuals who were heterozygous for the P376L variant (hazard ratio, 2.08; 95% CI, 1.12-to 3.84, p = 0.02). Although there was no association between the presence of the P376L variant and HDL-C level, serum HDLox, measured as dysfunctional HDL, was 13% higher among carriers of the P376L variant than non-carriers. CONCLUSION: We have found that carriers of the P376L variant possessed higher HDLox and were at increased risk of CVD in a representative population-based cohort, as compared to non-carriers.