الفهرس 
THROMBOSISOnly 14 pages are availabe for public view
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Abstract
Thrombosis, involving either the venous or the arterial systems, is one of the major causes of morbidity and mortality. Thrombosis, either alone or together with atherosclerotic vascular disease, is an underlying cause of myocardial infarctions, strokes, pulmonary embolism, and deep vein thrombosis (Feinbloom and Bauer, 2005).
Thrombophilia is being recognized as an increased tendency towards thrombosis through enhanced coagulation. Hereditary and acquired thrombotic risk factors continue to be the focus of active research and interest, as investigators seek to understand their role in the development of vascular pathology, morbidity and mortality (Feinbloom and Bauer, 2005).
The most common polymorphism involved in the etiology of venous thrombosis is factor V Leiden (FVLeiden), where the guanine to adenine transition at nucleotide position 1691 in factor V gene. This causes a lack of the cleavage site for activated protein C, resulting in activated protein C resistance. Heterozygosity for FVLeiden increases the risk of venous thrombosis 3- to 8-fold, while homozygosity increases the thrombotic risk 50- to 100-fold (Segers et al., 2007).
The second most prevalent polymorphism linked to thrombophilia is considered to be the Prothrombin G20210A where guanine to adenine transition at nucleotide position 20210 in the 3-untranslated region of the prothrombin gene resulting in increased plasma levels of prothrombin. The PT 20210A allele is associated with a 2- to 3-fold increased risk of venous thrombosis (Bosler et al.,2006). The third mutation is methylenetetrahydrofolate reductase (MTHFR) (C677T) is an enzyme involved in homocysteine metabolism and increased homocysteine levels, by depressing the activation of protein C, and was found to be a risk factor for venous thrombosis and stroke (Den Heijer et al.,2006).
The aim of the current study is detecting FVLeiden (G1691A), Prothrombin (G20210A), and mehtylenetetra-hydrofolate reductase (MTHFR) (C677T) by using multiplex PCR technique in patients with deep venous thrombosis and myocardial infarction, evaluating their relevance in thrombotic tendency and correlating the three genetic mutations with standard thrombotic risk factors.
Thirty patients and ten controls were included in this study. The control ages ranged from 24 to 66 years with a mean of 46±12.4. They were 7 males and 3 females with a male to female ratio of 2.3:1. Patients were divided into two groups: patients with deep venous thrombosis (Group I): 16 patients, they were 9 males and 7 females with a male to female ratio of 1.28:1. Their ages ranged from 23 to 64 years, with a mean of 43.5±13.2. Patients with myocardial infarction (Group II): comprised of 14 patients. They were 10 males and 4 females with a male to female ratio of 2.5:1. Their ages ranged from 32 to 67 years with a mean of 53.2±9.4.
The patients were subjected to the following: thorough history and clinical examination laying stress on family history, complete blood picture,activated partial thrmpoblastin time (APTT),estimation of standard risk factors for arterial and venous thrombosis, and multiplex PCR analysis for: Factor V Leiden (G1691A), Prothrombin (G20210A), and Mehtylen-etetrahydrofolate reductase (MTHFR) (C677T).
In the current study, all subjects of the control group (100%) had the normal genotype of prothrombin and MTHFR enzyme. Nine of them (90%) had normal FV genotype while only 1 (10%) was heterozygous for FVLeiden mutation.
Among group I (16 patients) molecular examination revealed that 13 patients (81.2%) were heterozygous for FVLeiden (G1691A), while 3 (18.8%) were homozygous for this mutation. None of the patients in this group had the normal FV genotype. Ten patients (62.4%) were heterozygous for prothrombin (G20210A) mutation, 3 patients (18.8%) were homozygous for it, while 3 patients (18.8%) had the normal genotype of this mutation. For MTHFR (C677T) mutation, none of the patients had normal genotype, while 14 patients (87.5%) were heterozygous and 2 (12.5%) were homozygous for this mutation.
On studying the association between the three studied prothrombotic genes with established risk factors for venous thrombosis, there was a significant association among both homzygous FVLeiden and homozygous Prothrombin (G20210A) with recurrent attacks of DVT. On the other hand, there were no significant association regarding heterozygous FVLeiden, heterozygous Prothrombin (G20210A) and MTHFR (C677T) noted with established risk factors.
Among group II (16 patients), 9 patients (64.3%) were heterozygous for FVLeiden (G1691A), 5 (35.7%) had normal FV genotype, while none of them was homozygous for this mutation. Ten patients (71.4%) were heterozygous and 3 patients (21.4%) were homozygous for prothrombin (G20210A) mutation, and only 1 patient (7.2%) had normal FII genotype. As regards MTHFR (C677T) mutation, none of the patients was homozygous for this mutation, 11 patients (78.6%) were heterozygous, while 3 (21.4%) had the normal genotype.
In this work, upon correlating the three studied prothrombotic genes with established risk factors for arterial thrombosis, there was a significant association among heterozygous FVLeiden (G1691A) and family history, while there was no significant association between homozygous FVLeiden, Prothrombin (G20210A), MTHFR (C677T) and other established risk factors.
In the current study, a unique characteristics that distinguish the patients having heterozygosity in the three studied genes from the rest of patients in each group were noticed. In group I, patients having combined heterozygosity in the 3 prothrombotic genes tend to be < 45 years, having more recurrent attacks, smokers, and more associated with females taking oral contraception. In group II, patients having combined heterozygosity in the 3 prothrombotic genes, tend to have inferior wall infarction, hypercholesterolaemia, hypertension, diabetis. Smoking and oral contraception is apparantly associated.
from this study it is noteworthy to conclude that:
The three prothrombotic genes { FVLeiden (G1691A), prothrombin (G20210A), and MTHFR (C667T)} could be considered an important marker for thrombosis either arterial or venous especially in presence of other conventional risk factors and in young patients. Moreover, the multiplex reaction is ideal for conserving costly polymerase and templates in short supply