Mutations and polymorphisms in genes affecting hemostasis proteins and homocysteine metabolism in children with arterial ischemic stroke.
BACKGROUND
The pathogenesis of thrombosis in childhood seems to be multifactorial implicating genetic and environmental factors.


OBJECTIVE
To compare the distributions of mutations/polymorphisms in genes affecting hemostasis (factor V Leiden - FVL, FV H1298R-FVR2, FII 20210A, b-Fib 455G>A, FXIII V34L, PAI-1 4G, HPA-1b) or homocysteine metabolism (MTHFR C677T, MTHFR A1298C) among 90 children with arterial ischemic stroke (AIS) and 103 controls, and to associate the carriage of these mutations/polymorphisms with their corresponding proteins in children with AIS.


RESULTS
AIS was more frequent in boys (p < 0.01). No studied mutation/polymorphism was found to be a risk factor for AIS, except for FVL [odds ratio 4.2 (95% CI 1.5-12.1)], the presence of which was even higher in 31 children with congenital AIS [odds ratio 6.82 (95% CI 2.0-22.8)]. FVL carriers had an odds ratio of 5.76 (95% CI 1.6-6.4) when FVR2 was absent. In thrombosed children, activated protein C resistance, prothrombin and fibrinogen levels were higher in the presence of FVL, FII20210A or b-Fib 455G-->A, respectively. Double heterozygotes in both MTHFR C677T and A1298T or homozygotes in one had significantly elevated homocysteine levels.


CONCLUSIONS
Except for FVL, no definite conclusion could be reached regarding the involvement of the studied mutations/polymorphisms in childhood AIS.
Hemostasis and Hemophilia Unit, Aghia Sophia Children's Hospital, Athens, Greece.
A
A
Komitopoulou
H
H
Platokouki
Z
Z
Kapsimali
H
H
Pergantou
E
E
Adamtziki
S
S
Aronis
D000483:Alleles; D002545:Brain Ischemia / Q000150:complications* / Q000235:genetics*; D002675:Child, Preschool; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D005165:Factor V / Q000235:genetics; D005260:Female; D005838:Genotype; D006487:Hemostasis / Q000235:genetics*; D006710:Homocysteine / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation / Q000502:physiology*; D016017:Odds Ratio; D011110:Polymorphism, Genetic / Q000502:physiology*; D012307:Risk Factors; D020521:Stroke / Q000209:etiology* / Q000235:genetics*
C095381:factor V Leiden; D006710:Homocysteine; D005165:Factor V; D004247:DNA