engleski

Synergistic effect of elevated lipoprotein (a) levels with inherited thrombophilia risk factors in children with arterial ishemic stroke

Background: Elevated lipoprotein (a) [Lp(a)] has been identified as a genetically determined risk factor for stroke in young adults. Recently, Sultan et al. (Int J Stroke 2014 ; 9:79–87) has also demonstrated a significant positive association between Lp(a) and arterial ischemic stroke (AIS) in children, whereas Kenet et al. (Circulation 2010 ; 21:1838–47) showed the highest odds ratio for combined genetic traits in first AIS onset. Aims: The aim was to investigate whether elevated Lp(a) levels are more frequently asssociated with already known inherited thrombophilia risk factors in children with a confirmed diagnosis of AIS. Methods: Study population comprised 61 children with AIS (perinatal n = 30, childhood n = 31). Lp(a) concentration was determined using a Tina-quant Lipoprotein(a) assay on Cobas c501 (Roche Diagnostics, Switzerland). Genotype analysis of FV Leiden, FV HR2, FII G20210A, b-fibrinogen -455G>A, FXIII-A Val34Leu, PAI-1 4G/5G, MTHFR C677T, MTHFR A1298C, ACE I/D, and apoE e2-4 was performed using a multilocus genotyping assay (CVD Strip Assay, ViennaLab, Austria). Human platelet alloantigens -1, -2, -3 and -5 were detected by ASO-PCR (Kluter et al. Vox Sang 1996 ; 71:121–5). Results: Children with AIS were divided into Lp(a) positive group (>0.3 g/ L) consisting of 16 (26%) children (median: 0.62 g/L), and Lp(a) negative group (<0.3 g/ L) consisting of 45 (74%) children (median: 0.09 g/L ). Elevated Lp(a) levels were statistically significantly associated with homozygosity for MTHFR A1298C (P = 0.036) and apo e2e3 genotype (P = 0.024). Unexpectedly, none of 7 identified FV Leiden carriers and 3 FV Leiden/FV HR2 heterozygotes were in the Lp(a) positive group, but their frequency was not statistically significant (P = 0.174 and P = 0.556, respectively). Conclusion: Among investigated inherited thrombophilia risk factors elevated Lp(a) levels may suggest synergistic effect with MTHFR 1298CC and apo e2e3 genotype and possible increased risk for AIS onset.

Lp(a), stroke, children, inherited thrombophilia

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