Statin and MTHFR C677T Polymorphism in Patients with Cardiovascular Diseases

Abstract

Objective: Cardiovascular disease (CVD) is the leading cause of death worldwide. The methylenetetrahydrofolate reductase (MTHFR) gene, located on the short (p) arm of chromosome 1 at position 36.3 (1p36.3), might be a possible risk factor for the pharmacogenetics in CVD. A common polymorphism in MTHFR (C677T, Ala→Val) decreases this enzyme activity and increases the homocysteine concentrations, predisposing one to heart disease. Alternatively, statins, cholesterol-reducing agents, are also used to reduce the homocysteine blood concentrations; the aim of the present study was to evaluate how the genotype frequencies of the MTHFR C677T polymorphism, namely rs1801133, change in the cardiovascular system in patients treated with statin. Methods:In this study, the genotype distribution of the MTHFR C677T polymorphism in CVD patients treated with statin (hydrophilic and lipophilic) (n=290) and healthy controls (n=151) was assessed using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Results:In this study, a statistically significant difference in genotype frequencies for the MTHFR C677T polymorphism was found between CVD patients treated with statin and controls (p=0.037). Yöntemler: Bu çalışmada, lipofilik ve hidrofilik statinler ile tedavi edilen kardiyovasküler sistem hastalarında (n=290) ve sağlıklı kontrollerde (n=151) MTHFR C677T polimorfizmindeki genotip dağılımları incelenmiştir. Genotipleme, Polimeraz zincir reaksiyonu (PCR) ve restriksiyon parça uzunluk polimorfizm (RFLP) yöntemi ile yapılmıştır. Bulgular: Bu çalışmada, MTHFR C677T polimorfizminin genotip dağılımında statin tedavisi gören kardiyovasküler sistem hastaları ile kontrol grubu arasında istatistiksel olarak anlamlı bir fark gözlenmiştir (p=0,037). ConclusionSonuç: Türk popülasyonunda statin ile tedavi edilen kardiyovasküler sistem hastaları ile MTHFR C677T polimorfizmi arasında istatistiksel olarak anlamlı bir ilişki ilk kez gösterilmiştir.

A pharmacogenetic pilot study reveals MTHFR, DRD3, and MDR1 polymorphisms as biomarker candidates for slow atorvastatin metabolizers

“…found that the MTHFR -rs1801133 C/C genotype protects against coronary heart disease in different populations [ 33 ]. Another study reported that the C/C genotype protected against cardiovascular disease in a Turkish population under statin therapy [ 34 ]. The C allele frequencies reported in both studies [ 33 , 34 ] are different from the allele frequencies found in the Mexican population.…”

“…Another study reported that the C/C genotype protected against cardiovascular disease in a Turkish population under statin therapy [ 34 ]. The C allele frequencies reported in both studies [ 33 , 34 ] are different from the allele frequencies found in the Mexican population. The MTHFR -rs1801133 polymorphism (C677T) causes an Ala → Val substitution which decreases enzyme activity leading to increased homocysteine levels.…”

“…The MTHFR -rs1801133 polymorphism (C677T) causes an Ala → Val substitution which decreases enzyme activity leading to increased homocysteine levels. Hyperhomocysteinemia is a known risk factor for cardiovascular disease [ 34 ]. How the T variant of MTHFR -rs1801133 augments ATV clearance, so that the drug response is diminished, remains to be elucidated.…”