ABSTRACT
BACKGROUND: Many studies have focused on the significance of lipid regulatory genes in the pathophysiology of Coronary artery disease (CAD). ApoB XbaI (rs693) and EcoRI (rs1042031) single nucleoid polymorphisms (SNPs) were investigated to detect whether they are risk factors for CAD. Till now, this association remains uncertain. SMARCA4 (rs1122608) SNP has directly related to dyslipidemia. Loss of function mutations (LOF) in PCSK9 result in a reduction in LDL cholesterol and are associated with protection from the development of CAD. METHODS: This study was conducted on 54 CAD patients who were admitted at Internal Medicine Specialized Hospital (Cardiology Department) and 47 healthy controls. Peripheral blood samples were taken from both groups. DNA was extracted from EDTA-blood samples, then PCR- RFLP for ApoB XbaI (rs693) and EcoRI (rs1042031), SMARCA4 (rs1122608) and PCSK9 (rs505151) SNPs was done. RESULTS: No statistically significant difference was found between patients and controls as regard EcoRI SNP. XbaI (rs693) X + X + genotype was significantly higher in control group (P = 0.0355). SMARCA4 (TT, GT + TT) genotypes, and T allele (P < 0.001); PCSK9 AG genotype and G allele (P = 0.027 and 0.032 respectively) were more frequent in CAD patients than controls. CONCLUSION: SMARCA4 (rs1122608) and PCSK9 (rs505151) SNPs are significantly accompanying with the risk of CAD development in the Egyptian population. X + X + genotype appeared to have a protective effect against CAD. However, no observed association between EcoRI (rs1042031) and the risk of CAD development was found.
Subject(s)
Coronary Artery Disease , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide , Proprotein Convertase 9 , Receptors, LDL , Humans , Coronary Artery Disease/genetics , Proprotein Convertase 9/genetics , Polymorphism, Single Nucleotide/genetics , Egypt/epidemiology , Female , Male , Middle Aged , Receptors, LDL/genetics , Case-Control Studies , Apolipoproteins B/genetics , Risk Factors , Aged , Genotype , Genetic Association Studies , Adult , Gene Frequency/genetics , Alleles , North African People , Apolipoprotein B-100ABSTRACT
BACKGROUND: Coronary artery disease (CAD) is the main cause of death in Egypt. Many LDL-R gene locus single nucleotide polymorphisms (SNP) are found to be associated with the risk of CAD. This research aimed to assess the allelic and genotypic frequencies of rs1122608 SNP and their association with the extent of vessel affection and lipid profile in a population of Egyptians.100 CAD patients and 100 healthy controls of Egyptians were included. PCR-RFLP was used to genotype rs1122608 SNPs. RESULTS: Significantly higher proportion of 'T' allele among patient (risk allele). This association is of low strength (Ï lies between 0.1 and 0.3). A participant with 'T' allele has 1.95 times higher odds to exhibit CAD versus a participant with 'G' allele. Significantly higher proportion of 'T/T' genotype among cases versus control (risk genotype). This association is of low strength (Cramer's V lies between 0.1 and 0.3). A participant with 'T/T' genotype has 4.5 times higher odds to exhibit CAD versus a participant with 'G/G'. Gensini score showed no significant association with rs1122608 genotypes (p = 0.863). CONCLUSIONS: The mutant GT and TT genotypes and minor T allele of rs1122608 were positively correlated with CAD and considered as independent risk factors for CAD.
ABSTRACT
Ca2+ signaling plays crucial role in ischemia and reperfusion (I/R) injury. Although blockade of L-type Ca2+ channels by amlodipine (AML) has been shown to suppress hepatic I/R injury in several animal models, information is still needed regarding the hepatoprotective effects of the dual L/N-type Ca2+ channel blockers, cilnidipine (CIL). We examined the effect of pretreatment with AML or CIL (100 µg/kg i.p.) 45 min before induction of 60 min of liver ischemia followed by reperfusion, on oxidative stress markers, liver enzymes, serum tumor necrosis factor-α, interleukin-1ß, apoptosis markers, and nuclear factor KB after 6 and 24 h of hepatic reperfusion. Both drugs significantly ameliorated biochemical and histological markers of hepatic I/R injury, but protection with CIL was more significant at the 6-h time point where protection with AML outlasted that of CIL. Both drugs offered significant protection against hepatic I/R damage, but the protection with CIL seemed more potent but of shorter duration than that observed with AML possibly due to the shorter half-life of CIL.
