Gene Polymorphisms Affect the Effectiveness of Atorvastatin in Treating Ischemic Stroke Patients

Abstract

Background/Aims: The aim of the present study is to investigate whether the single nucleotide polymorphism (SNP) in lipid metabolism related genes would affect the effectiveness of atorvastatin in both Han and Uighur populations. Methods: 200 ischemic stroke patients were treated with atorvastatin. The differences of blood lipid level and their ratios were measured. Six lipid related genes, HMGCR, APOA5, LPL, CETP, LDLR and PCSK9 were selected as candidate genes. And nine SNP loci in these six genes were genotyped by SNaPshot technique. Results: In all patients treated with atorvastatin, the SNP rs662799 significantly affected the ratio of ΔLDL and ΔLDL/LDL (p < 0.05); the SNP rs320 significantly affected the ratio of ΔLDL/LDL and Δ(LDL/HDL)/(LDL/HDL) (p < 0.01) and the SNP rs708272 significantly affected the ratio of ΔLDL (p < 0.05). In Han population treated with atorvastatin, the SNP rs662799 significantly affected the ratio of ΔTG (p < 0.05); the SNP rs320 significantly affected the ratio of ΔLDL/LDL and Δ(LDL/HDL)/(LDL/HDL) (p < 0.01). In Uighur population treated with atorvastatin, the SNP rs2266788 significantly affected the ratio of ΔHDL (p < 0.05); the SNP rs662799 significantly affected the ratio of ΔLDL/LDL (p < 0.05) and the SNP rs708272 significantly affected the ratio of ΔLDL (p < 0.05). Conclusion: Polymorphisms of rs662799 and rs2266788 in APOA5 gene, rs320 in LPL gene and rs708272 in CETP gene had significant association with the effect of the lipid-lowering therapy via atorvastatin calcium on ischemic stroke patients.

Tagging Functional Polymorphism in 3’ Untranslated Region of Methylene Tetrahydrofolate Reductase and Risk of Ischemic Stroke

“…The 677TT allele was also associated with elevated tHcy levels, predominantly in individuals with low plasma folate levels. Higher tHcy concentrations have in turn been shown to have a negative effect on stroke [16, 19]. …”

“…Functional polymorphisms in the exon region of the MTHFR have been shown to be associated with the pathogenesis of IS. For example, the rs1801133 polymorphism was associated with reductions in MTHFR activity of approximately 70% and 35% in TT and CT genotype carriers, respectively, leading to increased levels of tHcy, which predicted a poor prognosis among IS patients [14-16]. The A1298C variant resulted in substitution of glutamate (Glu) by alanine (Ala) at codon 429 in the S-adenosylmethionine regulatory domain of the MTHFR protein [17-19].…”

Atorvastatin Calcium Inhibits PDGF-ββ-Induced Proliferation and Migration of VSMCs Through the G0/G1 Cell Cycle Arrest and Suppression of Activated PDGFRβ-PI3K-Akt Signaling Cascade

“…Moreover, statins have also been reported to have a broad spectrum of biological activities, such as anti-oxidation, anti-inflammation and anti-thrombosis [21-24]. Although studies have demonstrated that statins can reduce intimal hyperplasia and slow atherosclerosis progression via inhibiting VSMCs proliferation and migration [25], the mechanisms behind the favorable effects of atorvastatin calcium on VSMCs are still not fully understood.…”

MiR-298 Exacerbates Ischemia/Reperfusion Injury Following Ischemic Stroke by Targeting Act1

“…Stroke is a primary cause of disability and mortality worldwide [1], and is often treated by intravenous or intra-arterial thrombolysis [2]. Temporary cessation of blood flow to the OGD/R model N2a cells were incubated in glucose-free DMEM and immediately transferred to a humidified atmosphere of 1% O 2 , 94% N 2 , and 5% CO 2 at 37°C for 1 h. Reoxygenation for 12, 24, 48, 72, or 96 h was initiated by rapidly replacing the glucosefree DMEM with normal medium and culturing the cells under normal conditions.…”