Park K S, Park J H, Song Y W
Department of Biology, Institute of Basic Science, Sungshin Women's University, Seoul, Korea.
Tissue Antigens. 2008 Oct;72(4):342-6. doi: 10.1111/j.1399-0039.2008.01110.x. Epub 2008 Aug 12.
The inhibitory (NKG2A) and activating (NKG2D and NKG2C) natural killer (NK) cell receptors are expressed on a subset of NK and T cells. They regulate the innate and adaptive immune systems related to cytotoxicity and cytokine production that are involved in the pathogenesis of rheumatoid arthritis (RA). The role of inhibitory and activating NK cell receptor genes might contribute to chronic inflammation and destruction of bone and cartilage in RA. Therefore, we investigated the association of the NKG2A, NKG2C, and NKG2D genotypes with RA. NKG2A (KLRC1) NKG2C (KLRC2), and NKG2D (KLRK1, D12S249E) genes were genotyped in 210 unrelated patients with RA and 298 controls using a polymerase chain reaction-restriction fragment length polymorphism. We further investigated the relationships between the genotypes of each single nucleotide polymorphism and the presence of rheumatoid factor (RF), antinuclear antibody (ANA), and bony erosions in RA patients. The major NKG2A c.338-90*A/A, NKG2C102Ser/Ser, and NKG2D72Ala/Ala genotypes in RA were significantly associated compared with controls [P = 0.013, odds ratio (OR) = 0.6, 95% confidence interval (CI) = 0.44-0.91; P < 0.0001, OR = 2.1, 95% CI = 1.44-2.96; and P = 0.019, OR = 0.6, 95% CI = 0.45-0.93, respectively]. The minor NKG2A c.338-90G/G, NKG2C102Phe/Phe, and NKG2D72Thr/*Thr genotypes showed a risk of RA (P = 0.010, OR = 2.0, 95% CI = 1.17-3.54; P < 0.0001, OR = 0.2, 95% CI = 0.12-0.48; and P = 0.032, OR = 2.3, 95% CI = 1.05-5.01, respectively) compared with controls. No significance was observed between the inhibitory (NKG2A) or activating (NKG2C and NKG2D) receptor genotypes and the presence of RF, ANA, or bony erosions in RA.
抑制性（NKG2A）和激活性（NKG2D及NKG2C）自然杀伤（NK）细胞受体在一部分NK细胞和T细胞上表达。它们调节与细胞毒性及细胞因子产生相关的固有免疫和适应性免疫系统，而这些过程参与类风湿关节炎（RA）的发病机制。抑制性和激活性NK细胞受体基因的作用可能促成RA中慢性炎症以及骨骼和软骨的破坏。因此，我们研究了NKG2A、NKG2C和NKG2D基因分型与RA的关联。采用聚合酶链反应-限制性片段长度多态性方法，对210例无亲缘关系的RA患者和298例对照进行了NKG2A（KLRC1）、NKG2C（KLRC2）和NKG2D（KLRK1，D12S249E）基因的基因分型。我们进一步研究了每个单核苷酸多态性的基因型与RA患者中类风湿因子（RF）、抗核抗体（ANA）以及骨侵蚀之间的关系。与对照组相比，RA患者中主要的NKG2A c.338 - 90*A/A、NKG2C102Ser/Ser和NKG2D72Ala/Ala基因型有显著相关性[P = 0.013，比值比（OR）= 0.6，95%置信区间（CI）= 0.44 - 0.91；P < 0.0001，OR = 2.1，95% CI = 1.44 - 2.96；以及P = 0.019，OR = 0.6，95% CI = 0.45 - 0.93]。次要的NKG2A c.338 - 90G/G、NKG2C102Phe/Phe和NKG2D72Thr/*Thr基因型显示出患RA的风险（与对照组相比，P分别为0.010，OR = 2.0，95% CI = 1.17 - 3.54；P < 0.0001，OR = 0.2，95% CI = 0.12 - 0.48；以及P = 0.032，OR = 2.3，95% CI = 1.05 - 5.01）。在RA患者中，未观察到抑制性（NKG2A）或激活性（NKG2C和NKG2D）受体基因型与RF、ANA或骨侵蚀的存在之间有显著关联。
