Rs7574865 polymorphism in signal transducers and activators of transcription 4 gene and rheumatoid arthritis: an updated meta-analysis of 28 case-control comparisons

Abstract

Objectives: The objective of the present meta-analysis was to investigate whether the combined evidence shows an association between the STAT4 rs7574865 polymorphism and RA.

Methods: A systematic search of all relevant studies published through April 2013 was conducted using MEDLINE, EMBASE, OVID, and ScienceDirect. The observational studies that were related to an association between the STAT4 rs7574865 polymorphism and RA were identified. The association between the STAT4 rs7574865 polymorphism and RA susceptibility was assessed using genetic models.

Results: Seventeen case-control studies with a total of 28 comparisons (25 300 RA patients and 26 326 controls) met the inclusion criteria. A meta-analysis was conducted for genotype TT versus GT+GG, GT+TT versus GG, TT versus GG and T-allele. The meta-analysis showed an association between RA and the STAT4 rs7574865 TT genotype, GT+TT genotype and T-allele in all subjects. Stratification of RA patients according to ethnic group showed that the TT genotype, GT+TT genotype and T-allele were significantly associated with RA in Europeans, Asians, Africans and Latin Americans. A subgroup analysis according to the absence or presence of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies revealed that the association between the STAT4 rs7574865 polymorphism and RA may be independent of the presence of RF and anti-CCP antibodies.

Conclusions: This meta-analysis demonstrated that the STAT4 rs7574865 polymorphism confers susceptibility to RA in major ethnic groups. The association may not be dependent on the presence of RF and anti-CCP antibodies.

Keywords: STAT4 transcription factor; meta-analysis; polymorphism; rheumatoid arthritis.