Lack of association between the prothrombin rs1799963 polymorphism and juvenile myoclonic epilepsy

Abstract

Juvenile myoclonic epilepsy (JME) is a subtype of common idiopathic generalized epilepsy (IGE) and accounts for 10% of all forms of epilepsy and up to 26% of IGE. Onset is at puberty with equal sex ratio and it is characterized by myoclonic jerks, occasional generalized tonic-clonic seizures, and sometimes absence seizures 1 . It is also highly drug-dependent, since a ABSTRACTJuvenile myoclonic epilepsy (JME) accounts for 26% of generalized idiopathic epileptic syndromes. The highest levels of thrombin activity are closely involved in the development of neurological diseases, including epilepsy. The prothrombin c.20210G>A (rs1799963) variation, which alters prothrombin mRNA stability, is associated with high plasma prothrombin levels. Objective: The present study was designed to investigate whether the SNP rs1799963 is a risk factor for JME in the northeastern Brazilian population. Results: The polymorphism was genotyped in 207 controls and 123 patients using polymerase chain reaction-restriction fragment length polymorphism method. No significant differences were observed in the genotype and allele frequencies of this polymorphism between cases and controls. Conclusion: These results present no evidence for an association of rs1799963 with JME. Further studies including other types of epilepsy are required to investigate the involvement of prothrombin gene in the genetic susceptibility to chronic seizure.Keywords: polymorphism, prothrombin, juvenile myoclonic epilepsy. RESUMOEpilepsia mioclônica juvenil (EMJ) representa 26% das síndromes epilépticas idiopáticas generalizadas. Níveis elevados de atividade da trombina estão intimamente envolvidos no desenvolvimento de distúrbios neurológicos, incluindo epilepsia. A variante c.20210G>A (rs1799963) do gene de protrombina, que altera a estabilidade do RNAm, está associada com altos níveis de protrombina no plasma. Objetivo: Investigar se o SNP rs1799963 é um fator de risco para EMJ em uma amostra da população do nordeste brasileiro. Resultados: O polimorfismo foi genotipado em 123 pacientes e 207 controles usando a reação de polimerase em cadeia com restrição de polimorfismo. Não observamos diferença significativa nas frequências alélicas e genotípicas deste polimorfismo, entre as populações de pacientes e controle. Conclusão: Estes resultados não demonstram evidências para uma associação do polimorfismo rs1799963 com EMJ. Estudos posteriores, incluindo outros tipos de epilepsia, são necessários para investigar o envolvimento do gene protrombina na susceptibilidade genética a crises crônicas.Palavras-chave: polimorfismo, protrombina, epilepsia mioclônica juvenil. 290Arq Neuropsiquiatr 2015;73(4):289-292 frequent recurrence is reported after antiepileptic drugs (AED) discontinuation 2 . Genetic factors are known to play an important role in the etiology of JME. Despite the existence of rare mutations responsible for some familial forms inherited in a mendelian pattern, the genetics of JME is complex and probably reflect the simultaneous involvement of multiple genes...

Genetic susceptibility in Juvenile Myoclonic Epilepsy: Systematic review of genetic association studies

“…Ninety-eight percent of them clearly define the study population[34–78,80–83]. In relation to representativeness of the controls, fifty-six percent were either population–based or healthy volunteers[36,38–42,45,46,48,51–53,55,58,62–65,67,69–72,74,77,80,82,83] and forty-five percent were both population-based and hospital-based/healthy volunteers/blood donors[34,35,37,43,44,47,49,50,54,56,57,59–61,66,68,73,75,76,78,79,81]. Sixty four percent of control matched only one variable (age, gender or ethnicity) with cases[36–40,42–48,50–54,56,57,62,66,68,69,71,73,75–79,81,82].…”

“…The majority (80%) did not perform genotyping under “blind” conditions (or did not mentioned this aspect). Results of HWE analysis were reported in 70% of the studies[36–41,43,45–47,49–53,55,56,58–60,62–65,67–72,74,76–78,82]. Ninety percent of the studies assessed the association between genotypes and JME using X 2 test and logistic regression, according to Clarke et al[84][34–39,41–53,55–68,70–78,80–82].…”