Shen Li, Zhang Hui, Zhou Xindie, Liu Ruiping
Department of Clinical Laboratory, Changzhou First People's Hospital, Changzhou 213003, China.
Department of Orthopaedics, Affiliated Hospital of Nanjing Medical University, Changzhou Second People's Hospital, Changzhou 213003, China.
Cytokine. 2015 Dec;76(2):363-367. doi: 10.1016/j.cyto.2015.09.007. Epub 2015 Sep 12.
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.
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.
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).
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.
本研究旨在探讨中国人群中白细胞介素12（IL-12）基因多态性与类风湿关节炎（RA）相关生物标志物之间的关联。
我们对中国人群中的615例RA患者和839例对照进行了IL-12A rs2243115 T/G和IL-12B rs3212227 A/C基因多态性研究。采用定制的48重SNPscan™试剂盒进行基因分型。通过酶联免疫吸附测定法检测了90例RA患者和90例对照的血浆IL-12水平。医生提供了具有其他潜在诊断价值的临床数据。
在类风湿因子（RF）阴性患者中，IL-12A rs2243115 GG基因型（GG与TT相比：OR = 4.81，95% CI 1.33 - 17.36，P = 0.017；GG与TG + TT相比：OR = 4.55，95% CI 1.27 - 16.36，P = 0.020）与RA风险显著增加相关；在老年患者（OR = 1.48，95% CI 1.06 - 2.06，P = 0.020）、RF阳性患者（OR = 1.35，95% CI 1.04 - 1.75，P = 0.026）和抗环瓜氨酸肽抗体（ACPA）阴性患者（OR = 1.53，95% CI 1.11 - 2.10，P = 0.009）中，IL-12B rs3212227 AC基因型（AC与AA相比）和AC + CC基因型（AC + CC与AA相比）与RA风险显著相关。RA患者的血浆IL-12水平显著更高（P < 0.001）。RA患者中IL-12A rs2243115 TT（P < 0.001）和IL-12B rs3212227 C等位基因（P < 0.001）的血浆IL-12水平分别显著高于对照。RF阳性RA患者的血浆IL-12水平显著高于RF阴性患者（P = 0.008），尤其是rs3212227 AC患者（P = 0.01）。
这些发现表明，功能性单核苷酸多态性（SNP）IL-12A rs2243115 GG基因型可能增加RF阴性患者患RA的风险，而IL-12B rs3212227 AC和AC + CC基因型与老年患者、RF阳性患者和ACPA阴性患者的RA风险相关。IL-12A rs2243115 T/G和IL-12B rs3212227 A/C等位基因也可能影响RA患者中IL-12的炎症反应。
