title: Association between polymorphisms of interleukin 12 and rheumatoid arthritis associated biomarkers in a Chinese population.
abstract: BACKGROUND
  The 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.
  
  
  METHODS
  We 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.
  
  
  RESULTS
  A 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).
  
  
  CONCLUSIONS
  These 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.
authors.affiliation: Department of Clinical Laboratory, Changzhou First People's Hospital, Changzhou 213003, China.
authors.forename: Li
authors.initials: L
authors.lastname: Shen
authors.affiliation: Department of Orthopaedics, Affiliated Hospital of Nanjing Medical University, Changzhou Second People's Hospital, Changzhou 213003, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedics, Affiliated Hospital of Nanjing Medical University, Changzhou Second People's Hospital, Changzhou 213003, China.
authors.forename: Xindie
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Orthopaedics, Affiliated Hospital of Nanjing Medical University, Changzhou Second People's Hospital, Changzhou 213003, China; Central Laboratory, Changzhou Second People's Hospital, Affiliated Hospital of Nanjing Medical University, Changzhou 213003, China. Electronic address: lrp216@sina.com.
authors.forename: Ruiping
authors.initials: R
authors.lastname: Liu
mesh_terms: D000328:Adult; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D015415:Biomarkers / Q000097:blood*; D002681:China; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D018664:Interleukin-12 / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: D015415:Biomarkers; D018664:Interleukin-12
keywords: Biomarker; Genetic; Interleukin 12; Polymorphism; Rheumatoid arthritis