The Impact of MicroRNA Gene Polymorphisms on Immune Response to Diphtheria Vaccine in Iraqi Children and Adolescents

Abstract

Background:Sinceitsinventioninthefirstquarterofthelastcentury,diphtheriatoxoidwas successfully used for vaccination against diphtheria. However, sporadic case and evenan epidemichavebeenrecordedinmanypartsoftheworld,suggestingthepresenceofgenetic factors influencing the immune response to thisvaccine.Aim: To assess the role of three single nucleotide polymorphisms(miRNA-146a G> C, miRNA-49T>GandmiRNA-196a2C>T)inmiRNAgenesinimmuneresponsetodiph- theriavaccine.SubjectsandMethods:Thisstudyrecruited68childrenandadolescentswhoreceived threedosesofdiphtheriatoxoid.DNAwasisolatedfromthebloodlymphocytesandmiRNA- 146a,miRNA-149 and miRNA-196a2 genes were amplified, and then directly sequenced. Serumlevelsofanti-diphtheriatoxoidsIgGantibodiesweredeterminedbyenzymelinked immunosorbent assay, and accordingly the immune response was categorized into good, moderate and low immunity .The association of different genotypes and alleles with immune statuswasillustratedstatistically.Results:Goodimmuneresponsetodiphtheriavaccinewassignificantlyassociatedwith the C allele of the polymorphism miRNA-146a G> C. Out of 14 carriers of GG geno- type,11(78.57%)showedgoodimmunitycomparedtoonly48.15%ofGGcarrierswhohad suchimmunity(P=0.039).ThemutantalleleofmiR-149T>Gwasmoreprevalentthanwild typealleleGamongsubjectswithgoodimmunity.However,thedifferencewasinsignificant.GenotypesandallelefrequenciesoftheSNPmiR-196a2C>Twereverycloseindifferent immunologicalstatuses.Conclusion:TheresultsofthecurrentstudysuggestthesignificantroleofmiRNA-146a G>CgenepolymorphismandtheinsignificantroleofbothmiRNA-149T>GandmiRNA- 196a2 C>T gene polymorphisms in response to diphtheria toxoids vaccine. More studies arerequiredtofindouttheassociationsofdifferentpolymorphismsinmiRNAgeneswith immune response for differentvaccines.