Interleukin-6 -572C/G polymorphism is associated with serum interleukin-6 levels and risk of idiopathic pulmonary arterial hypertension.

Interleukin 6 (IL-6) is a multifunctional proinflammatory cytokine that is elevated in patients with pulmonary arterial hypertension (PAH). Single nucleotide polymorphisms in the promoter region of IL-6 have been reported to transcriptional regulate the expression of IL-6. The aim of the present study is to investigate the roles of two common polymorphisms (-572C/G [rs1800796] and -6331T/C [rs10499563]) of IL-6 in idiopathic PAH (IPAH). A total of 338 IPAH patients and 352 age- and gender-matched healthy controls were enrolled. Genotyping of the two polymorphisms was performed by polymerase chain reaction and direct sequencing. Serum IL-6 levels were determined by ELISA assay. The frequencies of -572C/G genotypes CC, CG, and GG were found to be 63.6%, 32.3%, and 4.1% in IPAH patients group and 51.7%, 39.5%, and 8.8% in the controls, respectively. Compared with the individuals carrying the common genotype CC, the individuals carrying the GG genotype had a decreased risk of IPAH (adjusted odds ratio, 0.40; 95% confidence interval, 0.20-0.77; P = .006). The CG genotype and G allele carriers (CG/GG genotypes) were also observed to be associated with decreased risks of IPAH. Moreover, we found that individuals harboring -572GG or GC genotype showed significantly lower IL-6 levels than those harboring the -572CC genotype. No association between -6331T/C polymorphism and risk of IPAH or IL-6 levels was found. These results suggest that IL-6 promoter polymorphism -572C/G, but not -6331T/C, is associated with serum IL-6 levels and risk of IPAH.