Association of the carriage of <i>BRD2</i> rs206787 and rs516535 and <i>GJD2</i> rs3743123 polymorphisms with juvenile myoclonic epilepsy in Caucasian patients of Siberia

In recent years, the genetics of juvenile myoclonic epilepsy (JME) has been actively studied; the association of JME with the carriage of polymorphic allelic variants of the BRD2 (EJM3 locus) and GJD2 (EJM2 locus) genes has been established. Objective: to establish risk factors for JME in terms of a genetic predisposition; specifically, polymorphic allelic variants rs206787 and rs516535 in the BRD2 gene and rs3743123 in the GJD2 gene. Patients and methods: Examinations were made in 79 patients with JME and in 150 healthy volunteers, who were Caucasian and resided in the Siberian Federal District (SFD) and underwent determination of the carriage of single nucleotide polymorphisms (SNPs) rs206787 and rs516535 in the BRD2 gene and rs3743123 in the GJD2 gene by real-time polymerase chain reaction. Results and discussion. In 2003, American scientists from New York showed that the alleles associated with the development of JME with an autosomal recessive inheritance pattern might be located in the BRD2 gene. Patients with JME are assumed to have an autosomal dominant inheritance pattern of mutations in the BRD2 gene. British scientists revealed that different populations were found to have an association of SNP rs3918149 and no relationship of BRD2 rs206787 to the development of JME in Caucasians, as well as ascertained local linkage disequilibrium in the BRD2 gene. Our investigation has established complete linkage disequilibrium between the loci in patients with JME and in healthy individuals and no association of the carriage of SNPs rs206787 and rs516535 in the BRD2 gene with the development of JME in the patients residing in the SFD (p &gt;0.05). German scientists studied the impact of SNP in the BRD2 gene on a predisposition to a photoparoxysmal response in patients with JME/genetic generalized epilepsy. Our investigation has indicated the association of the carriage of TT/TT haplotype for SNP rs206787 and rs516535 in the BRD2 gene with a photoparoxysmal response in patients with JME (odds ratio (OR), 3.6; 95% confidence interval (CI), 1.37–9.48; p=0.02). We have confirmed that in the studied sample, the carriage of the T allele in the GJD2 gene (rs3743123) in the homozygous form is associated with the development of JME in Caucasian patients residing in the SFD and is a risk factor for JME (OR, 2.66; 95% CI, 1.24–5.74; p=0.04). The clinically significant association of this SNP in the GJD2 gene with the development of JME had been also previously demonstrated in two independent studies conducted in the European populations in the UK and Germany. There is a rise in the proportion of homozygotes in JME patients versus the control group, suggesting that the 588T allele under consideration increases the risk for JME in the homozygous state in the autosomal recessive inheritance pattern. Conclusion. The findings suggest that it is necessary to genotype Caucasian patients with JME, who reside in Siberia, for determination of the carriage of the TT/TT haplotype in terms of the investigated SNPs in the BRD2 gene (EJM 3 locus) and the carriage the T allele (rs3743123) in the GJD2 gene via a personalized approach to predicting the course of JME, as well as for identification of persons at risk for JME in the families having a history of this disease