Factor V1691 G-A, Prothrombin 20210 G-A, and Methylenetetrahydrofolate Reductase 677 C-T Variants in Turkish Children With Cerebral Infarct

Abstract

Inherited gene defects related to the coagulation system have been reported as risk factors for ischemic stroke. These gene defects include a G-A transition at nucleotide 1691 in exon 10 of the Factor V gene causing activated protein C resistance; a G-A transition in the 3' untranslated region of the prothrombin gene at nucleotide position 20210 (G-A), which is associated with increased levels of prothrombin activity; and a C-T polymorphism at nucleotide 677 in the methylenetetrahydrofolate reductase gene responsible for an alanine to valine substitution, resulting in the synthesis of a thermolabile form of methylenetetrahydrofolate reductase that causes increased levels of homocysteine. The case-control study included 28 patients with cerebral infarction; all were 18 years of age or younger (range, 10 months to 18 years). Seven (25%) of the 28 patients were heterozygous for the FV1691 mutation. Five (17.8%) of the patients carried the PT20210A mutation. Two (7.1%) of the patients carried both mutations. When compared to controls, the difference was significant for both mutations (P = .007; .04). The frequency of allele T of methylenetetrahydrofolate reductase 677 was 0.3214, which was not significant when compared to controls (0.231; P = .3). A total of 12 (42.8%) patients carried one or both of the mutations FV1691 G-A and PT20210 G-A. From our data, it appears that FV1691 G-A and PT20210 G-A are associated with cerebral infarct risk independently. Risk assessment of double prothrombotic gene alterations did not reveal synergy between these mutations. In conclusion, the presence of FV1691 A and PT20210 A mutations but not the methylenetetrahydrofolate reductase 677 TT mutation correlate with the occurrence of cerebral infarction in children.

Homozygous thermolabile variant of the methylenetetrahy‐drofolate reductase gene: a potential risk factor for hyperhomo‐cysteinaemia, CVD, and stroke in childhood

“…who were t-MTHFR homozygotes in a Turkish childhood stroke population and no difference in frequency from control individuals (Akar et al 1999). On the other hand, Cardo and colleagues (2000) found that nearly 30% of Spanish children with stroke were t-MTHFR homozygotes, twice as many as the control population, although this did not achieve statistical significance and the relation with homocysteine levels was not clear.…”

MTHFR C677T polymorphism and its relation to ischemic stroke in the Black Sea Turkish population

“…This mutation has been shown to be the most prevalent hereditary cause of venous thrombosis [28]. However, the roles described for MTHFR in arterial vascular disease and particularly cerebrovascular disease are contradictory [2,16,17,21,[29][30][31][32][33]. Lopaciuk et al [17] from Poland reported that homozygosity for C677T mutation in the MTHFR gene is not associated with an increased risk for ischemic stroke.…”

“…Elevated plasma levels of homocysteine have been established as a risk factor for vascular disease [16]. MTHFR (EC 1.5.1.20) involved in folate metabolism catalyzes the formation of 5-methylentetrahydrofolate from 5,10-methylentetrahydrofolate, which is the predominant circulatory form of folate and a carbon donor for remethylation of homocysteine to methionine [17][18][19].…”

New in vitro effects of clopidogrel on platelets in hyperlipidemic and healthy subjects

“…Based on our findings, the increase in platelet activation, apoptosis, oxidative status (MDA), aggregation, altered platelet membrane binding features, and decreased platelet nitrite levels in hyperlipidemia might elevate thrombotic risk causing atherogenesis to progress. New risk assessment criteria for thrombosis and cardiovascular diseases [42,43] and new drugs [44,45] for inhibition of coagulation are very important research areas. Clopidogrel is a drug that has been used for the secondary prevention of atherothrombotic events related to ischemia [46].…”