Abstract
BackgroundMutation in SCARB1 gene, exon 8 rs5888, has been associated with altered lipid levels and cardiovascular risk in humans though the results have been inconsistent. We analysed the impact of SCARB1 single nucleotide polymorphism (SNP) rs5888 with plasma lipid profile and association with coronary artery disease (CAD) in a Lithuanian population characterized by high morbidity and mortality from CAD and high prevalence of hypercholesterolemia.MethodsThe study included 1976 subjects from a random sample (reference group) and an myocardial infarction (MI) group of 463 patients. Genotyping of SCARB1 (rs5888) was carried out using the real-time polymerase chain reaction method.Results/principal findingsAnalysis of rs5888 C/T gene polymorphism in the reference group revealed that male TT genotype carriers (25–74 years) had significantly higher total cholesterol and triglyceride concentrations (5.70 mmol/l vs. 5.49 mmol/l; p = 0.036, and 1.70 mmol/l vs. 1.40 mmol/l, p = 0.023, respectively) than CT carriers and the oldest males (65–74 years) TT carriers had significantly higher high density lipoprotein cholesterol concentrations in comparison to heterozygous (1.52 mmol/l vs. 1.36 mmol/l, p = 0.033). The youngest female (25–44 years) TT genotype carriers had significantly lower low density lipoprotein cholesterol concentrations in comparison to C homozygous (2.59 mmol/l vs. 2.92 mmol/l, p = 0.023). The frequency of the SCARB1 TT genotype in the oldest male MI group (65–74 years) was significantly lower than in the corresponding reference group subjects (9.4% vs. 22.3%, p = 0.006). SCARB1 TT genotype was associated with decreased odds of MI in males aged 65–75 years (OR = 0.24, 95% CI 0.10-0.56, p = 0.001).Conclusions/significanceSCARB1 polymorphism is associated with lipid metabolism and CAD in an age- and gender- dependent manner. Analysis of SCARB1 SNP rs5888 C/T genotypes revealed an atheroprotective phenotype of lipid profile in older men and in young women TT genotype carriers in the reference group. SCARB1 TT genotype was associated with decreased odds of MI in aged men.
Highlights
Mutation in Scavenger receptor Class B Type 1 gene (SCARB1) gene, exon 8 rs5888, has been associated with altered lipid levels and cardiovascular risk in humans though the results have been inconsistent
SCARB1 is a multiligand receptor binding other native lipoproteins such as (i) low density lipoprotein (LDL); (ii) very low density lipoprotein (VLDL) [4]; and (iii) a variety of ligands, including modified lipoproteins, anionic phospholipids and apoptotic cells [4,5]. These receptors that were initially found in cultured macrophages [6], are highly expressed in the liver and in steroidogenic tissues [7]; their expression is regulated by a number of factors including estrogens [8,9,10,11,12,13], dietary cholesterol [14] and genetic variation [13,15]
The importance of SCARB1 in overall cholesterol metabolism and its antiatherogenic activity in vivo has been definitively established by SCARB1 gene manipulation in mice [6]
Summary
Mutation in SCARB1 gene, exon 8 rs5888, has been associated with altered lipid levels and cardiovascular risk in humans though the results have been inconsistent. SCARB1 is a multiligand receptor binding other native lipoproteins such as (i) low density lipoprotein (LDL); (ii) very low density lipoprotein (VLDL) [4]; and (iii) a variety of ligands, including modified (acetylated or oxidized) lipoproteins, anionic phospholipids and apoptotic cells [4,5] These receptors that were initially found in cultured macrophages [6], are highly expressed in the liver and in steroidogenic tissues [7]; their expression is regulated by a number of factors including estrogens [8,9,10,11,12,13], dietary cholesterol [14] and genetic variation [13,15]. Mutation in SCARB1 gene, exon 8 rs5888, has been associated with altered lipid levels and cardiovascular risk in humans [19,21,24], the results have been inconsistent [16,18,21,22,23]
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