P202 – 2912: Methylenetetrahydrofolate reductase (MTHFR) polymorphisms A1298C and C677T as genetic risk factors for perinatal and childhood arterial ischemic stroke?

Abstract

Objective The knowledge of arterial ischemic stroke (AIS) risk factors is still insufficient. Most frequently reported risk factors are cerebral arteriopathies, cardiac diseases, vascular malformations, infections, and traumas. Because of multifactorial etiology AIS might possibly have a multigenic inheritance pattern. The potential genetic risk factor for AIS could be the decreased activity of methylenetetrahydrofolate reductase (MTHFR), which is caused by common polymorphisms C677T (rs1801133) and A1298C (rs1801131). The aim of the study is to examine the role of these two MTHFR polymorphisms in searching for genetic determinants in arterial ischemic stroke. Methods 78 randomly selected pediatric stroke patients, 50 with perinatal and 28 with childhood stroke, participated in the study. Population-based control-group for perinatal stroke consisted of 150 and for childhood stroke of 84 healthy individuals. DNA testing for MTHFR C677T and A1298C mutations was performed, genotypes were determined by PCR using specific primers. Association analysis (p-values with Fisher exact test, odds ratios with 95% confidence intervals) was performed using Terminal software. Results The 677T allele carrier status (p=0.9, OR=1.0) did not show relevance as a genetic risk factor for perinatal stroke. An interesting observation was the fact that minor allele frequency of A1298C was higher in healthy controls than in patients with either perinatal (p=0.08, OR=0.63) or childhood (p=0.14, OR=0.6) AIS. On the other hand, minor allele frequency of C677T demonstrated a weak association with childhood AIS (p=0.09, OR=1.7, 95% CI: 0.9–3.2). Conclusion Our data support the hypothesis that functional MTHFR polymorphism C677T may represent a genetic risk factor for childhood AIS, representing 1.7-times higher risk. The A1298C polymorphism was not found as genetic risk factor for perinatal nor for childhood stroke.