Genetic polymorphisms in the interleukin 6 gene (IL-6) and its promoter regions have extensively been studied because of their potential role in the pathogenesis of rheumatoid arthritis (RA). Due to the confounding results, reported in several studies, we performed the systematic literature search on IL-6 -572 G/C polymorphism (rs1800796 SNP) and assessed its association with RA in the overall world population, and in the subgroup analysis of Asian and Caucasian populations. The results showed that in overall population, IL-6 -572 G/C shows a significant association towards increased risk of RA in allelic (OR=0.8130, 95%CI=0.708-0.932, p=0.003), co-dominant and dominant models; same hold true for the Asian population. Stratification by ethnicity revealed that in Asian population also, the association with RA manifestation is significant. However, in a cohort of 200 RA and 176 healthy subjects (n=376) from Pakistan, significant association between IL-6 -572 G/C polymorphism and progressive RA could not be established despite the fact that GG genotype exhibited higher susceptibility (p=0.088) towards RA in comparison with the CC counterpart (p=0.803). Further, using STRING software, we tried to elucidate the interconnection between different ILs and their combinatorial effect on the RA development and/or progression. In conclusion, our study suggests that the analyses of single- and multiple nucleotide polymorphisms in larger cohorts, originating from diverse ethnic groups, are imperative to ascertain the genetic contributors of RA in a specific population.