Association between polymorphisms of interleukin 12 and rheumatoid arthritis associated biomarkers in a Chinese population

• We examined the association between IL 12 polymorphisms and RA.
• IL-12A polymorphisms might increase the risk of RA in RF negative patients.
• IL-12B polymorphisms were associated with older, RF positive ACPA negative RA patients.
• The alleles might impact the inflammatory reaction of IL-12 in patients with RA.

IntroductionThe aim of the present study was to examine the association between polymorphisms of interleukin 12 (IL-12) and rheumatoid arthritis (RA) associated biomarkers in a Chinese population.Materials and methodsWe studied IL-12A rs2243115 T/G and IL-12B rs3212227 A/C polymorphisms in 615 RA patients and 839 controls in a Chinese population. Genotyping was done by a custom-by-design 48-Plex SNPscan™ Kit. The plasma level of IL-12 was measured by an enzyme-linked immune-sorbent assay in 90 RA patients and 90 controls. Clinical data with other potential diagnostic value were provided by the physicians.ResultsA significantly increased risk for RA associated with the IL-12A rs2243115 GG (GG versus TT: OR = 4.81, 95% CI 1.33–17.36, P = 0.017; and GG versus TG + TT: OR = 4.55, 95% CI 1.27–16.36, P = 0.020) genotype was evident among rheumatoid factor (RF) negative patients, and with the IL-12B rs3212227 AC (AC versus AA) and AC + CC (AC + CC versus AA) genotypes were evident among older patients (OR = 1.48, 95% CI 1.06–2.06, P = 0.020), RF positive patients (OR = 1.35, 95% CI 1.04–1.75, P = 0.026) and anti-cyclic citrullinated peptide antibodies (ACPA) negative patients (OR = 1.53, 95% CI 1.11–2.10, P = 0.009). The plasma level of IL-12 was significantly higher in RA patients (P < 0.001). IL-12 plasma level of IL-12A rs2243115 TT (P < 0.001) and IL-12B rs3212227 C allele (P < 0.001) were significantly higher in RA patients than controls respectively. The plasma level of IL-12 of RF positive RA patients was significantly higher than RF negative patients (P = 0.008), especially in rs3212227 AC patients (P = 0.01).ConclusionsThese findings suggested that the functional single nucleotide polymorphism (SNP) IL-12A rs2243115 GG genotype may increase the risk of RA in RF negative patients, and the IL-12B rs3212227 AC and AC + CC genotypes are associated with RA risk in older patients, RF positive patients and ACPA negative patients. The IL-12A rs2243115 T/G and IL-12B rs3212227 A/C allele might also impact the inflammatory reaction of IL-12 in patients with RA.