ABSTRACT
Objectives: ATP-binding cassette transporter A1 [ABCA1] plays a pivotal role in reverse cholesterol transport from peripheral tissues back to the liver. Abnormalities in ABCA1 function may lead to dyslipidemia and coronary artery disease [CAD]. We investigated the role of C-565T [rs2422493] promoter polymorphism of ABCA1 gene in the development and severity of CAD in an Iranian subpopulation
Methods: Our study population consisted of 110 angiographically-confirmed CAD patients and 110 matched controls. The severity of CAD was expressed based on the number of stenotic vessels. Genotyping of C-565T promoter polymorphism was performed using the polymerase chain reaction followed by restriction fragments length polymorphism analysis methods. Lipid profile was determined by routine colorimetric methods
Results: The distribution of ABCA1 C-565T genotypes [p = 0.035] and alleles [p = 0.017] was significantly different between the CAD and control groups. In univariate analysis [with genotype CC as reference], the TT genotype was significantly associated with an increased risk of CAD [odds ratio = 3.83; 95% confidence interval: 1.29-11.30, p = 0.014], but the CT genotype was not [p = 0.321]. A multiple binary logistic regression analysis revealed that smoking, hypertension, triglyceride, cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and ABCA1 C-565T dominant genotype were significant and independent risk factors for CAD development [p < 0.050]. The ABCA1 C-565T polymorphism affected the severity of CAD in TT homozygote state [p = 0.028]. However, no significant correlation was seen between this common polymorphism and lipid profile in the study population [p > 0.050].
Conclusions: Our study indicated that ABCA1 C-565T polymorphism is a significant risk factor for development and severity of CAD in our population.
ABSTRACT
Objectives: Organ-specific hemosiderosis and iron overload complications are more serious and more frequent in some patients with beta thalassemia major [BTM] compared with others. We investigated whether coinheritance of HFE H63D or C282Y gene mutations in patients with BTM contributes to the phenotypic variation of iron overload complications and assessed the correlation of cardiac and hepatic hemosiderosis with plasma ferritin levels
Methods: We studied 60 patients with BTM with a mean age of 17.5+/-9.1 years from the Northwest of Iran. HFE gene mutations were analyzed using the polymerase chain reaction-restriction fragment length polymorphism method. Cardiac and hepatic hemosiderosis was assessed using T2[asterisk]magnetic resonance imaging [MRI]. Ferritin levels were measured using the enzyme immunoassay method
Results: Ferritin levels showed a strong inverse correlation with hepatic T2[asterisk]MRI values [r = -0.631, p =0.001] but a poor correlation with cardiac T2[asterisk]MRI values [r = -0.297, p = 0.044]. The correlation between cardiac T2[asterisk]MRI values and hepatic T2[asterisk]MRI values was poor and insignificant [r = 0.287, p = 0.058]. Genotype and allele distribution of HFE H63D and C282Y mutation did not differ significantly between patients with and without hepatic or cardiac hemosiderosis [p > 0.050]. However, carriers of HFE 63D allele had significantly higher ferritin levels compared with non-carriers [1 903+/-993 vs. 992+/-683, p < 0.001]
Conclusions: Cardiac T2[asterisk]MRI values showed a poor correlation with hepatic T2[asterisk]MRI values and ferritin levels. Accurate assessment of cardiac iron overload in patients with BTM can only be done using the T2[asterisk]MRI technique. Additionally, HFE H63D is a significant determinant factor for elevated ferritin levels in BTM patients