Rare P376L variant in the SR-BI gene associates with HDL dysfunction and risk of cardiovascular disease
| Autor: | Gordon A. Ferns, Homa Falsoleiman, Mohsen Moohebati, Amir Avan, Sara Samadi, Habibollah Esmaily, Zeinab Sadat Hosseini, Maryam Tayefi, Zahra Farjami, Majid Ghayour-Mobarhan, Amir Hooshang Mohammadpour |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
Male 030213 general clinical medicine medicine.medical_specialty Clinical Biochemistry Population Disease 030204 cardiovascular system & hematology Gastroenterology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine High-density lipoprotein Risk Factors Diabetes mellitus Internal medicine medicine Humans Missense mutation education education.field_of_study Polymorphism Genetic Models Genetic business.industry Cholesterol HDL Hazard ratio General Medicine Middle Aged Scavenger Receptors Class B medicine.disease SCARB1 chemistry Cardiovascular Diseases Cohort Female Lipid Peroxidation business Follow-Up Studies |
| Zdroj: | Clinical Biochemistry. 73:44-49 |
| ISSN: | 0009-9120 |
| DOI: | 10.1016/j.clinbiochem.2019.06.014 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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