A Preliminary Association Study of H19 Non-Coding Gene Variants With Risk of Non-Hodgkin Lymphoma: A Case-Control Study and Computational Analysis

Background: Non-Hodgkin lymphoma (NHL) is one of the most prevalent disorders worldwide, with a variety range of etiology from environmental to genetic factors. H19 is a non-coding RNA that codes no protein while playing regulatory roles and is hypothesized to be involved in susceptibility to NHL. Methods: 209 NHL patients and 259 healthy subjects were studied. The salting out method was used for genomic DNA extraction, followed by the Refractory fragment length polymorphism polymerase chain reaction (RFLP-PCR) technique for genotyping. SPSS package V.22 software was used for statistical analysis. Several in silico tools were used to predict the probable consequences of studied H19 genetic variants on the different aspects of non-coding RNAs. Results: The results revealed that statistically, both rs3741219T>C and rs217727C>T variants increased the susceptibility to NHL. The T allele of rs3741219T>C in the codominant model caused the most enhancement in the incidence of NHL (OR = 2.33, 95% CI = 1.28-4.25, p = 0.005). Moreover, The CC genotype of rs217727C>T compared to TT had the sharpest impact on the susceptibility to NHL (OR = 2.27, 95% CI = 1.21-4.23, p = 0.009). In silico predictions revealed that the studied variants seem to alter the binding sites of miRNAs on the H19 long non-coding RNA and change its targets. Furthermore, nucleotide substitution in both rs3741219T>C and rs217727C>T may prepare a new binding site for a transcription factor called Y-Box-binding protein-1 (YB-1). Conclusions: The rs217727C>T and rs3714219T>C were responsible for elevating the likelihood of NHL in our population. These substitutions alter the RNA folding of H19 and alter the miRNA binding sites on the H19 transcript.