Gene variants and mRNA expression analysis of SOCS3 and its association with serum IL-4 levels in atopic diseases.

BACKGROUND: The suppressors of cytokine signaling (SOCS) are a class of negative regulators for several aspects of cytokine signaling that have been attributed to the pathophysiology of inflammatory disorders. Given the role of the SOCS3 gene in regulating Th2 cell proliferation, our study aimed to analyze two SOCS3 SNPs viz. rs8074003 and rs7222391, and their potential influence on IL-4 levels and SOCS3 mRNA expression besides analyzing the interaction of the SOCS3 genotypes with the various clinicopathological parameters. METHODS: A total of 314 subjects including 154 atopic cases and 160 healthy controls were genotyped for SOCS3 polymorphisms by PCR-RFLP. SOCS3 mRNA was quantified by Real-Time PCR. The serum IL-4 and total IgE levels were determined by ELISA and Vitamin-D levels were quantified by chemiluminescence. RESULTS: The CC genotype of rs8074003 was more frequent in atopic cases and posed a 3- fold risk of atopy (p = 0.001) whereas CG and GG genotypes were widespread in the controls (p = 0.1). For the other SNP rs7222391, there was no difference in genotypic and allelic distribution. The SOCS3 mRNA expression and serum IL-4 levels were substantially increased in the atopic cases with a significant positive correlation between them (p < 0.05). CONCLUSION: SOCS3 SNP rs8074003 poses a convincing risk of atopic disease development. The SOCS3 expression and IL-4 levels were up-regulated in total atopy and in its different presentations. It seems plausible to target SOCS3 and IL-4 as a potential target for the diagnosis of atopy and for the development of reliable personalized therapeutic strategies to control atopic conditions.