Dataset Information

Sex-Specific Influence of the SCARB1 Rs5888 SNP on the Serum Lipid Response to Atorvastatin in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention.

ABSTRACT: Background:Epidemiological studies have shown that there are sex differences in blood lipid levels and lipid responses to statins. Previous studies have shown that the rs5888 single nucleotide polymorphism (SNP) in the scavenger receptor class B type 1 (SCARB1) gene is associated with serum lipid levels in a sex-specific manner. The present study was undertaken to detect the sex-specific influence of the SCARB1 rs5888 SNP on the serum lipid response to atorvastatin in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Methods:A total of 158 unrelated ACS patients (108 males, 50 females) were enrolled, and all patients received atorvastatin 20 mg/daily after PCI. Genotyping of the rs5888 SNP was performed by polymerase chain reaction and direct sequencing. Serum lipid profiles were determined before treatment and after an average follow-up time of one year. Results:The baseline serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and apolipoprotein (Apo)AI levels were higher in females than in males (P<0.05). After treatment with atorvastatin, serum TC, LDL-C, and ApoB were decreased, and ApoAI was increased (P<0.05). The effects of atorvastatin on serum lipid levels were different between males and females, and females had greater decreases in TC, LDL-C and ApoB levels than males (P<0.05). The genotypic frequencies of the rs5888 SNP were not different between males and females. The atorvastatin response was not associated with the rs5888 SNP in males (P > 0.05). Nonetheless, in female individuals carrying the rs5888 T-allele, we observed a greater reduction in TC, LDL-C, and ApoB levels after the use of 20 mg/day atorvastatin (P<0.05). Conclusion:This study indicates that the SCARB1 rs5888 T-allele was associated with a greater reduction in serum TC, LDL-C, and ApoB after atorvastatin treatment in female patients with ACS undergoing PCI.

SUBMITTER: Wu DF

PROVIDER: S-EPMC7605962 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Sex-Specific Influence of the SCARB1 Rs5888 SNP on the Serum Lipid Response to Atorvastatin in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention.

Wu Dong-Feng DF Lin Dan D Lu Feng F Liao Qin-Chen QC Wu Yu-Juan YJ Wang Zhou Z Yu Kun K Li Wei-Jun WJ Deng Jin-Long JL

Pharmacogenomics and personalized medicine 20201029

<h4>Background</h4>Epidemiological studies have shown that there are sex differences in blood lipid levels and lipid responses to statins. Previous studies have shown that the rs5888 single nucleotide polymorphism (SNP) in the scavenger receptor class B type 1 (<i>SCARB1</i>) gene is associated with serum lipid levels in a sex-specific manner. The present study was undertaken to detect the sex-specific influence of the <i>SCARB1</i> rs5888 SNP on the serum lipid response to atorvastatin in patie ...[more]

PMID: 33154658

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Project description:BACKGROUND: 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. 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. METHODS: The 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 FINDINGS: Analysis 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/SIGNIFICANCE: SCARB1 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.

Project description:BackgroundBai Ku Yao is a special subgroup of the Yao minority in China. The present study was undertaken to detect the association of rs5888 single nucleotide polymorphism (SNP) in the scavenger receptor class B type 1 (SCARB1) gene and several environmental factors with serum lipid levels in the Guangxi Bai Ku Yao and Han populations.MethodsA total of 598 subjects of Bai Ku Yao and 585 subjects of Han Chinese were randomly selected from our stratified randomized cluster samples. Genotypes of the SCARB1 rs5888 SNP were determined by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing.ResultsThe levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein (Apo) AI were lower but ApoB was higher in Bai Ku Yao than in Han (P < 0.05-0.001). The frequencies of C and T alleles were 78.3% and 21.7% in Bai Ku Yao, and 73.7% and 26.3% in Han (P < 0.01); respectively. The frequencies of CC, CT and TT genotypes were 60.0%, 36.6% and 3.4% in Bai Ku Yao, and 54.2%, 39.0% and 6.8% in Han (P < 0.01); respectively. The subjects with TT genotype in both ethnic groups had lower HDL-C and ApoAI levels than the subjects with CC or CT genotype (P < 0.05 for all). Subgroup analyses showed that the subjects with TT genotype in Bai Ku Yao had lower HDL-C and ApoAI levels in males than the subjects with CC or CT genotype (P < 0.05 for all), and the T allele carriers had higher TC, LDL-C and ApoB levels in females than the T allele noncarriers (P < 0.05 for all). The participants with TT genotype in Han also had a lower tendency of HDL-C and ApoAI levels in males than the participants with CC or CT genotype, but the difference did not reach statistically significant (P = 0.063 and P = 0.086; respectively). The association of serum HDL-C and ApoAI levels and genotypes was confirmed by the multiple linear regression analysis in both ethnic groups. Serum lipid parameters were also correlated with several environmental factors.ConclusionsThe differences in serum lipid levels between the two ethnic groups might partially attribute to the differences in the SCARB1 rs5888 SNP and several environmental factors.

Project description:ImportanceLoading doses of atorvastatin did not show reduction on clinical outcomes in the overall population of patients with acute coronary syndrome (ACS) enrolled in the Statins Evaluation in Coronary Procedures and Revascularization (SECURE-PCI) trial, but a potential benefit was identified in patients who subsequently underwent percutaneous coronary intervention (PCI).ObjectivesTo determine whether periprocedural loading doses of atorvastatin are associated with decreased 30-day major adverse cardiovascular events (MACE) in patients with ACS undergoing PCI according to type of ACS and timing of atorvastatin administration before PCI.Design, setting, and participantsSecondary analysis of a multicenter, double-blind, placebo-controlled, randomized clinical trial conducted at 53 sites that enrolled 4191 patients with ACS intended to be treated with PCI between April 18, 2012, and October 06, 2017.InterventionsPatients were randomized to 2 loading doses of 80 mg of atorvastatin or matching placebo before and 24 hours after a planned PCI. By protocol, all patients (regardless of treatment group) received 40 mg of atorvastatin for 30 days starting 24 hours after the second dose of study medication.Main outcomes and measuresThe primary outcome was MACE through 30 days, composed by all-cause mortality, myocardial infarction, stroke, and unplanned coronary revascularization. Cox regression models adjusting for key baseline characteristics were used to assess the association between atorvastatin and MACE in patients undergoing PCI.ResultsFrom the overall trial population, 2710 (64.7%) underwent PCI (650 women [24.0%]; mean [SD] age, 62 [11.3] years). Loading atorvastatin was associated with reduced MACE at 30 days by 28% in the PCI group (adjusted hazard ratio [HR], 0.72; 95% CI 0.54-0.97; P = .03). Loading dose of atorvastatin was administered less than 12 hours before PCI in 2548 patients (95.3%) (45.1% < 2 hours and 54.3% between 2 and 12 hours). There was no significant interaction between treatment effect and timing of study drug administration. The treatment effect of loading atorvastatin was more pronounced in patients with ST-segment elevation myocardial infarction than in patients with non-ST-segment elevation ACS (adjusted HR, 0.59; 95% CI, 0.38-0.92; P = .02; HR, 0.85; 95% CI, 0.58-1.27; P = .43, respectively).Conclusions and relevanceIn patients with ACS undergoing PCI, periprocedural loading doses of atorvastatin appeared to reduce the rate of MACE at 30 days, most clearly in patients with ST-segment elevation myocardial infarction. This beneficial effect seemed to be preserved and consistent, irrespective of the timing of atorvastatin administration, including within 2 hours before PCI.Trial registrationclinicaltrials.gov Identifier: NCT01448642.

Dataset Information

Sex-Specific Influence of the SCARB1 Rs5888 SNP on the Serum Lipid Response to Atorvastatin in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention.

Publications

Sex-Specific Influence of the SCARB1 Rs5888 SNP on the Serum Lipid Response to Atorvastatin in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention.

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