Abstract

  Background and Objectives

 Fibrinogen, coagulation factor 1, is a soluble plasma glycoprotein which converts thrombin to fibrin fibers in the coagulation cascade. Various polymorphisms located on beta chain gene, FGB, have been studied. The promoter – G455A (rs1800790) polymorphism had been shown to be significantly associated with fibrinogen plasma levels. In this study, the frequency of rs1800790 ‎ polymorphism has been assessed and the correlation was evaluated between this variant and fibrinogen plasma levels.

  Materials and Methods

 Whole blood samples were collected for DNA isolation. To perform ‎ rs1800790 ‎ genotyping, the region encompassing the HaeIII restriction site was amplified using specific primers. The plasma levels of fibrinogen were measured and the obtained data were analyzed by SPSS software.

  Results

  The levels of plasma fibrinogen has shown a significant correlation with FGBrs1800790 ‎ genotype (p-value = 0.021 ‎ ‏ ‏ CI = 0 ‎ .347 ‎ ‏- ‎‎ 3.253). Minor allele frequency was estimated to be 0.28 which was consistent with the predicted value.

  Conclusions

  The significant correlation between fibrinogen and FGBrs1800790 ‎ genotype emphasizes the importance of this variant in the modulation of fibrinogen plasma concentrations. Since FGBrs1800790 ‎ contributes to the gene expression and environmental risk factors, it is important to be noticed in the cardiovascular disease.

 Abstract

 Background and Objectives

 Clopidogrel is one of the most commonly prescribed drugs to prevent ischemic events following coronary syndromes or stent placement. The objective of this study was to evaluate the prevalence of the cytochrome P450 (CYP450) 2C19 enzyme (CYP2C19) genotypes in the Iranian population.

 Materials and Methods

 CYP2C19 (*1/*2/*3) variants were analyzed using Polymerase Chain Reaction-Restriction Length Polymorphism (PCR–RFLP) assays in a representative sample of 154 Iranian patients with ischemic heart disease in Peyvand Laboratory. 

 Results

 In this study, out of 154 Iranian patients the frequency rates of CYP2C19 *2 were 36 (23.4%) in heterozygous and 6 (3.9%) in homozygous forms 112 (72.7%) patients had the normal genotype.

 Conclusions

 FDA recommendations are more useful to be practiced in our country than other countries. Physicians should identify patients and advise them to consider other antiplatelet medications or alternative dosing strategies in poor metabolizers.

  Abstract

 Background and Objectives

 Arterial thrombosis, with MI as the severe complication, represents the most frequent cause of death in the world. Although there is no doubt that genetic factors contribute significantly to the prothrombotic state, the data on polymorphisms in candidate genes are still inconclusive. We investigated if T13254C polymorphism in the platelet GPVI gene confers an increased risk of premature acute myocardial infarction (MI).

 Materials and Methods

 We conducted a case-control study of 100 young males with premature acute MI and 100 inpatient controls of the similar age, without any known heart diseases. Genotyping was done using PCR-RFLP. The significance of differences between cases and controls with respect to the variables was tested using student’s t test and Chi square. Logical regression model was used to control confounding variables.

 Results

 The allele frequencies of T13254C polymorphism did not differ between patients (30%) and controls (33%), and this polymorphism was not associated with premature acute MI (p < 0.05). Logistic regression analysis also indicated no association between these polymorphisms and premature MI.

 Conclusions

 Compatible with our study, the T13254C polymorphism of platelet collagen receptor did not play a significant role in the development of premature MI.

Abstract

Background and Objectives

Warfarin and other anticoagulant medications like Coumadin are widely prescribed by physicians to prevent ischemic events. A variety of factors such as sex, age and weight can affect warfarin dosage requirements. A clinical effect of warfarin depends on highly polymorphic drug-metabolizing (CYP2C9) enzymes. The objective of this study was to investigate the impact of CYP2C9*2, CYP2C9*3 polymorphisms on the variability of warfarin dosage requirements in Iranian population that were under warfarin therapy for different reasons.

Materials and Methods

The study included 100 patients with the mean age of 61.3 years. The restriction fragment length polymorphism method was used to identify polymorphisms of CYP2C9 (*1, *2, *3) in Iranian patients with ischemic heart disease in Peyvand Laboratory.

Results

Two-thirds (68.42%) of the patients had the wild-type (WT) CYP2C9*1*1 genotype 10.53%, 18.95%, and 2.1% of the patients had CYP2C9 *1*2, *1*3, and *2*3 genotype, respectively. WT CYP2C9*1*1 genotype was associated with a higher daily warfarin dosage (4.58 ± 1.57 mg/day  p= 0.02) as compared to other CYP2C9 genotypes.

Conclusions

The Iranian study sample is characterized by high frequency *1*1 genotypes that determine a higher warfarin-loading dose. Analysis of CYP2C9 gene variants allows the prediction of warfarin dosage. These results can be used to individualize treatment with warfarin in Iranian patients.

Key words: Warfarin, Genetic Polymorphism, CYP2C9 protein٬ human, Vitamin K

Abstract

Background and Objectives

Warfarin and other anticoagulant medications like Coumadin are widely prescribed by physicians to prevent ischemic events. A variety of factors such as sex, age and weight can affect warfarin dosage requirements. A clinical effect of warfarin depends on highly polymorphic drug-metabolizing (CYP2C9) enzymes. The objective of this study was to investigate the impact of CYP2C9*2, CYP2C9*3 polymorphisms on the variability of warfarin dosage requirements in Iranian population that were under warfarin therapy for different reasons.

Materials and Methods

The study included 100 patients with the mean age of 61.3 years. The restriction fragment length polymorphism method was used to identify polymorphisms of CYP2C9 (*1, *2, *3) in Iranian patients with ischemic heart disease in Peyvand Laboratory.

Results

Two-thirds (68.42%) of the patients had the wild-type (WT) CYP2C9*1*1 genotype 10.53%, 18.95%, and 2.1% of the patients had CYP2C9 *1*2, *1*3, and *2*3 genotype, respectively. WT CYP2C9*1*1 genotype was associated with a higher daily warfarin dosage (4.58 ± 1.57 mg/day  p= 0.02) as compared to other CYP2C9 genotypes.

Conclusions

The Iranian study sample is characterized by high frequency *1*1 genotypes that determine a higher warfarin-loading dose. Analysis of CYP2C9 gene variants allows the prediction of warfarin dosage. These results can be used to individualize treatment with warfarin in Iranian patients.

Key words: Warfarin, Genetic Polymorphism, CYP2C9 protein٬ human, Vitamin K

Abstract

Background and Objectives

Warfarin and other anticoagulant medications like Coumadin are widely prescribed by physicians to prevent ischemic events. A variety of factors such as sex, age and weight can affect warfarin dosage requirements. A clinical effect of warfarin depends on highly polymorphic drug-metabolizing (CYP2C9) enzymes. The objective of this study was to investigate the impact of CYP2C9*2, CYP2C9*3 polymorphisms on the variability of warfarin dosage requirements in Iranian population that were under warfarin therapy for different reasons.

Materials and Methods

The study included 100 patients with the mean age of 61.3 years. The restriction fragment length polymorphism method was used to identify polymorphisms of CYP2C9 (*1, *2, *3) in Iranian patients with ischemic heart disease in Peyvand Laboratory.

Results

Two-thirds (68.42%) of the patients had the wild-type (WT) CYP2C9*1*1 genotype 10.53%, 18.95%, and 2.1% of the patients had CYP2C9 *1*2, *1*3, and *2*3 genotype, respectively. WT CYP2C9*1*1 genotype was associated with a higher daily warfarin dosage (4.58 ± 1.57 mg/day  p= 0.02) as compared to other CYP2C9 genotypes.

Conclusions

The Iranian study sample is characterized by high frequency *1*1 genotypes that determine a higher warfarin-loading dose. Analysis of CYP2C9 gene variants allows the prediction of warfarin dosage. These results can be used to individualize treatment with warfarin in Iranian patients.

Abstract

Background and Objectives

Beta thalassemia is an autosomal recessive disease. The synthesis of HbF in patients with β-thalassemia seems to ameliorate the severity of symptoms.

Materials and Methods

In this case control study, 150 β-thalassemia major patients, 34 thalassemia intermedia patients, and 50 healthy individuals as the control were studied. HindIIIG polymorphism in IVSII-I Gγ gene was determined using RFLP-PCR method. HbF levels with electrophoresis method were taken from clinical files. Then, the linkage disequilibrium of this polymorphism with XmnI polymorphism in 5' Gγ gene was determined by D' Power Marker software.

Results

After data analysis, an association was observed between the A allele and thalassemia intermedia. In the dominant effect of the A allele (comparison between AA+AC vs. CC), AA+AC genotypes associates with intermedia thalassemia (p = 0.014, OR = 9.30, CI(95%) =   1.14-75.9) but there is no association with major thalassemia (p = 0.1, OR = 1, CI(95%) =  0.41-1.19). The means of HbF levels in β-thalassemia major and thalassemia intermedia patients were 94.3 g/dl and 84.4 g/dl, respectively. High linkage disequilibrium was seen between the two polymorphisms.

Conclusions

It is concluded that A allele may act as a dominant allele and increase disease amelioration. It showed that A allele of HindIIIG polymorphism has a positive effect on HbF level. Furthermore, the A allele of HindIIIG  polymorphism is strongly correlated with T allele of XmII polymorphism in thalassemia intermedia patients and C allele of HindIIIG  polymorphism is strongly correlated with C allele of XmnI polymorphism in β-thalassemia major.

Key words: beta-Thalassemia, Genetic Polymorphism, HBF,  Thalassemia Intermedia

Abstract

Background and Objectives

Human T-cell lymphotropic virus type 1 (HTLV-1) requires cell-to-cell communication to cause infection. The increase in the number of cells infected with virus in turn increases the likelihood of virus transmission and progression of disease. Host immune system responses and genetics factors can affect the susceptibility to virus. Thus, in this study, for the first time the polymorphism in PD-1 gene promoter, which is involved in the negative regulation of immune responses, was evaluated in the HTLV-1 asymptomatic carriers and the healthy controls in the Iranian population in 2020.

Materials and Methods

In this case-control study, genomic DNAs of 81 HTLV-1 asymptomatic carrier  blood donors and 162 healthy blood donors in Khorasan Razavi province were extracted and the rs36084323 polymorphisms  were genotyped with PCR- RFLP method. To confirm the genotyping results, PCR products were sequenced. The results were analyzed using SPSS-22 statistical software based on chi-square test.

Results

The frequencies of G and A alleles of rs36084323 polymorphism were 75% and 25% in the control group and 79.6% and 20.4% in the case group, respectively. Considering the G allele as a reference there was no significant difference between the case and control groups (p = 0.256).

Conclusions 

The results of this study showed that there is no association between G/A in single nucleotide polymorphism of rs36084323 with susceptibility to HTLV-1 virus infection in the Iranian population.