In silica analysis by Bioinformatics tools, Genotyping AND Linkage Disequilibrium of UGT1A6 Gene Polymorphism in Pediatric Epileptics and it’s influence on Sodium valproate Monotherapy

ABSTRACT: Introduction: Objective of the observational cohort study was to evaluate UGT1A6 gene polymorphisms and their association with sodium valproate monotherapy. The extent of linkage disequilibrium in pairwise combinations of single nucleotide polymorphisms (SNPs) were also calculated. Selection of the SNPs was carried out using bioinformatics tools. Methodology: Children aged 2-18 years diagnosed with epilepsy and treated with sodium valproate monotherapy were recruited. Five ml of venous blood sample was collected. EDTA samples were used to evaluate the gene polymorphism using PCR-RFLP method and serum sample used to estimate the serum drug concentration by HPLC. Linkage Disequilibrium was carried out using the SHEsisplus program platform. Results: Out of 231 missense mutations, three SNPs, rs1105879 (A552C) rs6759892 (T19G) and rs2070959 (A541G) were selected for the wet lab analysis. rs1105879 (A552C) was found to be deleterious with a SIFT score of 0.026. Apart from UGT1A6 (T19G) pattern, none of the genotype frequency distributions for UGT1A6 variants deviated significantly from HWE (P<0.05), suggesting that alleles were in equilibrium. There was no statistically significant association between patients of UGT1A6 (A552C, T19G, A541G) gene polymorphism and the therapeutic range of sodium valproate at different intervals (basal, six months, and one year).The SNPs of UGT1A6 showed a strong LD between T19G and A541G, A541G and A552C of UGT1A6. Of the pairwise haplotypes association, none were statistically significant except for a haplotype TAACGT, with a chi square value of 7.77, p=0.005, with OR 0.121 [95% CI =0.021~0.689]. This suggests a good response to therapy among these haplotypes. Conclusion: There was a higher pattern of mutant carrier alleles for the genes UGT1A6 (T19G, A541G, A552C). There was no association between the gene UGT1A6 and sodium valproate concentration although the mean concentration of sodium valproate was high in wild type of UGT1A6 (T19G, A541G, A552C).

ORGANISM(S): Homo sapiens (human)

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PROVIDER: S-BSST952 | biostudies-other |

REPOSITORIES: biostudies-other