The genetic variants in 3’ untranslated region of voltage-gated sodium channel alpha 1 subunit gene affect the mRNA-microRNA interactions and associate with epilepsyReportar como inadecuado

The genetic variants in 3’ untranslated region of voltage-gated sodium channel alpha 1 subunit gene affect the mRNA-microRNA interactions and associate with epilepsy - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

BMC Genetics

, 17:111

Statistical and computational genetics


BackgroundmRNA expression in a cell or subcellular organelle is precisely regulated for the purpose of gene function regulation. The 3’ untranslated region 3’UTR of mRNA is the binding target of microRNA and RNA binding proteins. Their interactions regulate mRNA level in specific subcellular regions and determine the intensity of gene repression. The mutations in the coding region of voltage-gated sodium channel alpha 1 subunit gene, SCN1A, were identified in epileptic patients and confirmed as causative factors of epilepsy. We investigated if there were genetic variants in 3’UTR of SCN1A, affecting the microRNA-mRNA 3’UTR interaction and SCN1A gene repression, potentially associated with epilepsy.

ResultsIn this case–control study, we identified twelve variants, NM 001202435.1:n.6277A > G, n.6568 6571del, n.6761C > T, n.6874A > T, n.6907 T > C, n.6978A > G, n.7065 7066insG, n.7282 T > C, n.7338 7344del, n.7385 T > A, n.7996C > T, and n.8212C > T in 3’UTR of SCN1A gene. We found that the variant of n.6978A > G in all our samples was completely mutated G-G. In male group, T allele in n.7282 T > C was associated with epilepsy, while C allele was significantly less frequent in epileptic patients than in normal males OR 0.424. Consequently, the haplotype -CTTACATGACGA- -CTC TA- was significantly less frequent in male epileptic patients 0.173 than in normal males 0.305. The frequency of haplotype block found in females -TTTAACA- -TTCAACA-, and -CTTAACA- was 0.499, 0.254 and 0.234 respectively. Within STarMir model analysis, the -CTCTA- haplotype showed significantly higher site accessibility to microRNA targeting and higher downstream sequence accessibility for nonconserved binding than that of other haplotypes. Overall, the male genotypes have the higher accessibility of the downstream 30nt block of nonconserved site than the female genotypes.

ConclusionsNM 001202435.1:n.7282 T > C is the genetic variant associated with epilepsy in males, and the related haplotype -CTTACATGACGA- -CTCTA- in the region of chr2: 165991297–165989081, which has high site accessibility for microRNA binding, is the genetic protective factor against epilepsy in males. In female subset, the frequencies of haplotype block -TTTAACA- -TTCAACA-, and -CTTAACA- were 0.499,0.254 and 0.234 respectively. Alleles and haplotypes distribution did not differ in female cases in comparison to female controls.

KeywordsEpilepsy Untranslated region microRNA SNP Haplotype Electronic supplementary materialThe online version of this article doi:10.1186-s12863-016-0417-y contains supplementary material, which is available to authorized users.

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Autor: Tian Li - Yaoyun Kuang - Bin Li


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