Impact of the -174G/C interleukin-6 (IL-6) gene polymorphism on the risk of paediatric ischemic stroke, its symptoms and outcome

Ischemic stroke remains one of the top ten causes of death in children. There is evidence for the role of pro-inflammatory cytokines, such as IL-6 and the -174G>C promoter polymorphism of the IL-6 gene, in the occurrence and outcome of stroke in adults. The aim of the present study was to determine a possible association between the -174G>C IL-6 polymorphism and occurrence of paediatric stroke, its symptoms and outcome. The study group consisted of 340 individuals: 80 stroke children, 122 parents of patients and 138 controls. The -174G/C polymorphism was genotyped using the RFLP method. For the analysis of the relationship between genotypes and stroke we used two alternative methods: the case-control model and the transmission test for linkage disequilibrium using data from families. We observed no differences in the transmission of alleles from parents to children. We also did not find any statistical differences in distribution of genotypes and alleles between patients and controls. However, the analysis showed that post-stroke epilepsy was genotype-dependent. All children with epilepsy were G allele carriers and none of them was a CC homozygote whereas about 25% of children without epilepsy had the CC genotype. Our study did not show any associations between the IL-6 -174 G>C polymorphism and the occurrence of stroke but we observed a relation between post-stroke epilepsy and the G allele carrier-state

Polimorfizm C242T genu kodującego cytochrom b-245 alfa nie jest związany z udarem niedokrwiennym mózgu u dzieci : analiza wewnątrzrodzinna i badanie kliniczno-kontrolne

Background and purpose: Reactive oxygen species play an important role in the physiology and pathology of cerebral arteries, including ischaemic stroke. The cytochrome b-245 alpha gene (CYBA) encodes cytochrome b-245 alpha light chain (p22phox peptide), a critical element of NAD(P)H oxidases, the most important source of superoxide anion in the cerebral arteries. To search for genetic factors associated with paediatric ischaemic stroke, the possible association between CYBA gene C242T polymorphism and the disease was evaluated. Material and methods: The study group consisted of 238 in - dividuals: children with ischaemic stroke (n = 70), their biological parents (n = 118) and children without any symptoms of stroke (n = 50). The C242T polymorphism was genotyped using polymerase chain reaction – restriction fragment length methodology. To evaluate the possible association between polymorphism and stroke, the transmission disequilibrium test and the case-control method were applied. Results: The C242 allele was transmitted more frequently than 242T (62.2% vs. 37.8%) but observed frequencies did not differ significantly from expected (p = 0.10). There were also no significant differences in allele and genotype distribution between patients and control subjects (patients: CC – 50.0%, CT – 38.6%, TT – 11.4% vs. controls: CC – 52.0%, CT – 36.0%, TT – 12.0%). Conclusions: The study did not show that the C242T polymorphism of the CYBA gene is a risk factor of ischaemic stroke in childre

Polimorfizm C242T genu kodującego cytohrom b-245 alfa nie jest związany z udarem niedokrwiennym mózgu u dzieci: analiza wewnątrzrodzinna i badanie kliniczno-kontrolne

Background and purpose Reactive oxygen species play an important role in the physiology and pathology of cerebral arteries, including ischaemic stroke. The cytochrome b-245 alpha gene (CYBA) encodes cytochrome b-245 alpha light chain (p22phox peptide), a critical element of NAD(P)H oxidases, the most important source of superoxide anion in the cerebral arteries. To search for genetic factors associated with paediatric ischaemic stroke, the possible association between CYBA gene C242T polymorphism and the disease was evaluated. Material and methods The study group consisted of 238 individuals: children with ischaemic stroke (n = 70), their biological parents (n = 118) and children without any symptoms of stroke (n = 50). The C242T polymorphism was genotyped using polymerase chain reaction – restriction fragment length methodology. To evaluate the possible association between polymorphism and stroke, the transmission disequilibrium test and the case-control method were applied. Results The C242 allele was transmitted more frequently than 242T (62.2% vs. 37.8%) but observed frequencies did not differ significantly from expected (p = 0.10). There were also no significant differences in allele and genotype distribution between patients and control subjects (patients: CC – 50.0%, CT – 38.6%, TT – 11.4% vs. controls: CC – 52.0%, CT – 36.0%, TT – 12.0%). Conclusions The study did not show that the C242T polymorphism of the CYBA gene is a risk factor of ischaemic stroke in children.Wstęp i cel pracy Reaktywne formy tlenu pełnią istotną funkcję zarówno w fizjologii, jak i patologii tętnic mózgowych, także w patogenezie udaru niedokrwiennego mózgu. Gen cytochromu b-245 alfa (gen CYBA) koduje lekki łańcuch cytochromu b-245 (białko p22phox), kluczowy składnik oksydaz NAD(P)H, najważniejszego źródła anionorodnika ponadtlenkowego w obrębie tętnic mózgowych. W niniejszej pracy, poszukując genetycznych czynników ryzyka predysponujących do udaru mózgu u dzieci, oceniano możliwe związki pomiędzy polimorfizmem C242T genu CYBA i chorobą. Materiał i metody W badaniu wzięło udział 238 osób: 70 dzieci z udarem niedokrwiennym mózgu, 118 ich biologicznych rodziców oraz 50 dzieci bez żadnych objawów udaru. Polimorfizm C242T genu CYBA genotypowano metodą polimorfizmu długości fragmentów restrykcyjnych w reakcji łańcuchowej polimerazy. Do oceny możliwych związków pomiędzy polimorfizmem i udarem zastosowano dwie niezależne metody: wewnątrzrodzinny test transmisji i badanie kliniczno-kontrolne. Wyniki Allel C242 był częściej przekazywany chorym dzieciom przez heterozygotycznych rodziców niż allel 242T (62,2% w porównaniu z 37,8%), jednak obserwowane częstości nie odbiegały znamiennie od oczekiwanych (p = 0,10). Nie wykazano także znaczących różnic w rozkładzie alleli i genotypów pomiędzy pacjentami i dziećmi z grupy kontrolnej (pacjenci: CC – 50,0%, CT – 38,6%, TT – 11,4%; grupa kontrolna: CC – 52,0%, CT – 36,0%, TT – 12,0%). Wnioski Wyniki badań nie wykazały, aby polimorfizm C242T genu CYBA był czynnikiem ryzyka udaru niedokrwiennego u dzieci