Lack of association between rs211037 of the GABRG2 gene and juvenile myoclonic epilepsy in Brazilian population

Gitaí, Lívia Leite Góes; Almeida, Delma Holanda de; Born, João Paulo Lopes; Gameleira, Fernando Tenório; Andrade, Tiago Gomes de; Machado, Luciana Cláudia Herculano; Gitaí, Daniel Leite Góes

doi:10.4103/0028-3886.105191

Cited by 15 publications

(17 citation statements)

References 23 publications

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“…Allele frequency for the GABRG2 rs211037/C588T/Asn196Asn polymorphism showed differences in geographic distribution, race and origin of selected populations. An allelic distribution similar to that found in our study was reported in populations of Japanese and Chinese origin, as well as some European populations, with the T allele being more frequently highlighted in those with seizures (either IGE, FS, or both); these results are inconsistent with allele frequencies identified in populations from India, Germany and Nigeria [ 37 – 39 ].…”

Section: Discussionsupporting

confidence: 59%

GABRG2 C588T gene polymorphisms might be a predictive genetic marker of febrile seizures and generalized recurrent seizures: a case-control study in a Romanian pediatric population

Butilă¹,

Zazgyva²,

Sin³

et al. 2018

aoms

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IntroductionThis case-control study aimed to assess two single nucleotide polymorphisms of the gene encoding the GABRG2 protein – GABRG2 (3145 G>A) and GABRG2 rs 211037 Asn196Asn (C588T) – in a cohort of pediatric patients from Romania, and evaluate their possible impact on drug-resistant forms of generalized epilepsy and recurrent febrile seizures.Material and methodsOne hundred and fourteen children with idiopathic generalized epilepsy (group 1) or febrile seizures (group 2) were compared to 153 controls. Peripheral blood samples were assessed using polymerase chain reaction-restriction fragment length polymorphism analysis, with results interpreted based on the disappearance of a restriction site in the C allele (122 bp) compared to the T allele (100 bp + 22 bp).ResultsA significant association was found with the TT homozygous genotype and T allele for both febrile seizures and epilepsy for the C588T locus, while GABRG2 G>A 3145 showed no significant association with any type of seizure. The TT homozygous genotype of GABRG2 Asn196Asn polymorphism was more frequent in patients with a history of febrile seizures (p = 0.0001), without a significant association identified for GABRG2-G>A 3145. Composite analysis showed associations with epilepsy for CC-AG (p = 0.02) and CT-AG (p = 0.007) with the CC-AA combination as reference.ConclusionsC588T polymorphism of the GABRG2 gene might be a predictive genetic marker in triggering febrile convulsions. GABRG2 rs211037 TT homozygotes and T allele variants have an increased risk for developing febrile seizures. Recurrent crises and repeated episodes of seizures are more frequent in the GABRG2 Asn196Asn TT genotype polymorphism, with a 45 and 8 times higher risk of developing idiopathic generalized epilepsy and recurrent febrile seizures, respectively.

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Section: Discussionsupporting

confidence: 59%

GABRG2 C588T gene polymorphisms might be a predictive genetic marker of febrile seizures and generalized recurrent seizures: a case-control study in a Romanian pediatric population

Butilă¹,

Zazgyva²,

Sin³

et al. 2018

aoms

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“…Demographic and clinical data of the unrelated patients with JME were reported previously [41]. Table 1 shows both allelic and genotypic frequencies of the studied polymorphisms in the two groups under study.…”

Section: Resultsmentioning

confidence: 99%

PER2 rs2304672, CLOCK rs1801260, and PER3 rs57875989 polymorphisms are not associated with juvenile myoclonic epilepsy

Santos¹,

Marques²,

Malta³

et al. 2014

Epilepsy & Behavior

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Sleep disturbance is common in several epilepsy types, such as juvenile myoclonic epilepsy (JME). Genetic background could increase susceptibility to seizure and sleep abnormalities. From this perspective, a susceptibility gene for sleep disturbance or chronotype could contribute to the genetic susceptibility threshold for epilepsy and vice versa. Accordingly, we investigated whether functional clock gene polymorphisms (PER2 111C>G, CLOCK 3111T>C, and PER3 VNTR) might influence the risk for JME. All these polymorphisms have recently been reported to be associated with sleep disturbance, diurnal variation, and neurological diseases. The polymorphisms were genotyped in 97 patients and 212 controls using polymerase chain reaction or restriction fragment length polymorphism methods. No significant differences were observed in the genotypic and allelic frequencies of these polymorphisms between cases and controls even when analyses were restricted to patients that presented a diurnal preferential seizure occurrence. We also tested for interactions between polymorphisms by multifactor dimensionality reduction analysis. None of the combined genotypes differed significantly between the groups. These results present no evidence for an association of these polymorphisms with JME. Further studies including other types of epilepsy and/or other functional polymorphisms are required to investigate the possible relationship between clock genes and the genetic susceptibility to chronic seizure.

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“…For example, GABRG2 (rs211037) had a significant association with an Indian population but not in a Brazilian population. Interestingly, the allele and genotype frequencies of these polymorphisms show wide variation between the populations investigated, suggesting a role for ethnic differences in the distribution of this variant[63]. In these cases, the lack of replication could be caused by differences in the genetic structure of populations investigated.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, even though most researchers followed the ILAE clinical criteria, inconsistent interpretation of clinical parameters and electrographic findings could still contribute to the divergent results. For example, Balan et al[71] only used abnormal findings on EEG recordings to support JME diagnosis, while Gitaí et al[63] included generalized spike-wave discharges in their diagnosis. Moreover, JME is a heterogeneous electroclinical epilepsy syndrome[91,92].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2017

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BackgroundSeveral genetic association investigations have been performed over the last three decades to identify variants underlying Juvenile Myoclonic Epilepsy (JME). Here, we evaluate the accumulating findings and provide an updated perspective of these studies.MethodologyA systematic literature search was conducted using the PubMed, Embase, Scopus, Lilacs, epiGAD, Google Scholar and Sigle up to February 12, 2016. The quality of the included studies was assessed by a score and classified as low and high quality. Beyond outcome measures, information was extracted on the setting for each study, characteristics of population samples and polymorphisms.ResultsFifty studies met eligibility criteria and were used for data extraction. With a single exception, all studies used a candidate gene approach, providing data on 229 polymorphisms in or near 55 different genes. Of variants investigating in independent data sets, only rs2029461 SNP in GRM4, rs3743123 in CX36 and rs3918149 in BRD2 showed a significant association with JME in at least two different background populations. The lack of consistent associations might be due to variations in experimental design and/or limitations of the approach.ConclusionsThus, despite intense research evidence established, specific genetic variants in JME susceptibility remain inconclusive. We discussed several issues that may compromise the quality of the results, including methodological bias, endophenotype and potential involvement of epigenetic factors.PROSPERO registration numberCRD42016036063

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Lack of association between rs211037 of the GABRG2 gene and juvenile myoclonic epilepsy in Brazilian population

Abstract: These results present no evidence for an association of rs211037 with JME. Further studies are required to investigate the involvement of the GABRG2 gene in the genetic susceptibility to this epileptic syndrome.

Cited by 15 publications

References 23 publications

GABRG2 C588T gene polymorphisms might be a predictive genetic marker of febrile seizures and generalized recurrent seizures: a case-control study in a Romanian pediatric population

GABRG2 C588T gene polymorphisms might be a predictive genetic marker of febrile seizures and generalized recurrent seizures: a case-control study in a Romanian pediatric population

PER2 rs2304672, CLOCK rs1801260, and PER3 rs57875989 polymorphisms are not associated with juvenile myoclonic epilepsy

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

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