ABSTRACT
This study investigated how 5'-UTR of DEFB1 gene (encoding for the human beta-defensin-1) affects mRNA secondary structure and its correlation with translation efficiency in the susceptibility of diseases. It was possible to determine DEFB1 mRNA folding under the influence of 5'-UTR SNPs haplotypes and putative alternative transcript lengths. Different DEFB1 mRNAs that fold in a pattern that is haplotype and length-dependent are potentially able to drive changes in peptide expression dynamics.
Subject(s)
5' Untranslated Regions/genetics , RNA, Messenger/genetics , beta-Defensins/metabolism , Alternative Splicing/immunology , Computer Simulation , Gene Expression Regulation/immunology , Haplotypes , Humans , Immunity, Innate , Nucleic Acid Conformation , Polymorphism, Single Nucleotide , Protein Binding/genetics , Protein Biosynthesis/genetics , Protein Biosynthesis/immunology , Software , Transcription Factors/metabolism , beta-Defensins/geneticsABSTRACT
We analyzed three functional 5' un-translated region beta-defensin 1 (DEFB1) single nucleotide polymorphism (SNPs) in a group of 170 type 1 diabetes (T1D) patients. In order to evaluate the SNPs influence on the disease onset and the development of other autoimmune disorder, such as celiac disease (CD) and autoimmune thyroid disease (AITD), patients were stratified according to the presence of AITD, CD, and both AITD and CD. As control group, we studied 191 healthy children and adolescent not presenting a familiar historic of T1D, CD or AITD. DEFB1 SNPs were in Hardy-Weinberg equilibrium both in healthy controls and T1D patients, as well in the T1D patients stratified according to the presence of other autoimmune disorder(s). Allele, genotype, and haplotype frequencies of T1D patients globally considered were comparable to healthy controls ones. No evidence of any association of DEFB1 SNPs with the onset of AIDT, CD, and both AITD and CD on T1D patients was evidenced. Only a minor trend was found for an increased frequency of the - 20 G allele in T1D patients only presenting AITD vs. T1D patients not presenting AITD or CD, as well as an increase of those haplotypes comprising the - 20 G allele when compared with the GCA haplotype. We also evaluated the influence of functional DEFB1 SNPs on the age of T1D onset: no significant statistical conclusion was achieved. Further studies are envisaged, in order to elucidate the possible role of functional DEFB1 polymorphisms in the onset of TD1 and other autoimmune-related disorders.
