Effect of rs1058240 polymorphism in 3'-UTR of GATA3 gene on potential binding of miRNAs and its association with RRMS risk: bioinformatics analysis and case-control study.

AIM

Multiple sclerosis is believed to be an autoimmune disease that is influenced by T helper (Th) cell differentiation. GATA3 plays an important role in reducing the development and severity of MS by shifting the differentiation of Th cells to Th2 and regulatory T cells while inhibiting the differentiation of Th1 and Th17 cells. Considering the functional role of rs1058240 SNP in the 3'-UTR of GATA3 mRNA, the association of target SNP with the risk of RRMS was examined.

METHODS

Genomic DNA was extracted from whole blood samples of 200 RRMS patients and 226 healthy individuals as a control group. Different genotypes of rs1058240 SNP were determined using the RFLP-PCR technique. Statistical analysis was performed using SPSS software and χ2 and logistic regression tests. The stability of GATA3 mRNA secondary structures and the binding patterns of GATA3-miRNAs with different alleles were evaluated using RNAfold and RNAhybrid programs, respectively.

RESULTS

The results indicated that the GATA3 rs1058240 G allele (p value = 0.010, OR = 1.45, CI = 1.09-1.93) and GG genotype (adjusted  = 0.017, OR = 2.27, 95%CI = 1.16-4.44) increased the risk of RRMS, particularly in women (adjusted  = 0.006, OR = 2.99, 95%CI = 1.37-6.52). Bioinformatics analysis revealed that although the allelic variation of this polymorphism had only a slight effect on mRNA stability (-177 to -177.20), the G allele significantly increased miRNA binding strength and miRNA-mRNA thermodynamic stability for hsa-miR-337-5p, hsa-miR-4445-3p, hsa-miR-4485-3p, hsa-miR-95-3p (ΔMFE > 0) compared to the A allele.

CONCLUSION

The G allele and GG genotype of rs1058240 in GATA3 mRNA 3'-UTR were found to be risk factors for increasing the susceptibility to RRMS.