Morgan A W, Griffiths B, Ponchel F, Montague B M, Ali M, Gardner P P, Gooi H C, Situnayake R D, Markham A F, Emery P, Isaacs J D
University of Leeds, UK.
Arthritis Rheum. 2000 Oct;43(10):2328-34. doi: 10.1002/1529-0131(200010)43:10<2328::AID-ANR21>3.0.CO;2-Z.
To investigate a possible association between a functional polymorphism in the intermediate-affinity receptor for IgG called Fc-gamma receptor type IIIA (FcgammaRIIIA [CD16]) and rheumatoid arthritis (RA).
This was an allelic association study in which a single nucleotide polymorphism in FcgammaRIIIA was examined as a susceptibility and/or severity factor for RA. The FcgammaRIIIA-158V/F polymorphism was genotyped by direct sequencing in 2 well-characterized ethnic groups, UK Caucasians (141 RA patients and 124 controls) and North Indians and Pakistanis (108 RA patients and 113 controls).
The FcgammaRIIIA-158V/F polymorphism was associated with RA in both ethnic groups (P = 0.028 for UK Caucasians, P = 0.050 for North Indians and Pakistanis, and P = 0.003 for both groups combined). FcgammaRIIIA-158VF and -158W individuals had an increased risk of developing RA in both populations (UK Caucasians odds ratio [OR] 1.6, P = 0.050; North Indians and Pakistanis OR 1.9, P = 0.023; and combined groups OR 1.7, P = 0.003). In the UK Caucasian group, the highest risk was for nodular RA, a more severe disease subset, associated with homozygosity for the FcgammaRIIIA-158V allele (OR 4.4, P = 0.004). There was also evidence for an interaction between the RA-associated HLA-DRB1 allele and the presence of at least 1 FcgammaRIIIA-158V allele in predicting susceptibility to RA (OR 5.5, P = 0.000).
We have demonstrated that the FcgammaRIIIA-158V/F polymorphism is a susceptibility and/or severity marker for RA in 2 distinct ethnic groups. This finding may ultimately provide additional insights into the pathogenesis of RA and other autoantibody/immune complex-driven autoimmune diseases.
研究免疫球蛋白G中间亲和力受体III型（Fcγ受体IIIA [CD16]）的功能多态性与类风湿关节炎（RA）之间可能存在的关联。
这是一项等位基因关联研究，其中检测Fcγ受体IIIA中的单核苷酸多态性作为RA的易感性和/或严重程度因素。通过直接测序对两个特征明确的种族群体（英国白种人（141例RA患者和124例对照）以及北印度人和巴基斯坦人（108例RA患者和113例对照））进行Fcγ受体IIIA - 158V/F多态性基因分型。
在两个种族群体中，Fcγ受体IIIA - 158V/F多态性均与RA相关（英国白种人P = 0.028，北印度人和巴基斯坦人P = 0.050，两组合并P = 0.003）。在两个人群中，Fcγ受体IIIA - 158VF和 - 158W个体患RA的风险均增加（英国白种人优势比[OR] 1.6，P = 0.050；北印度人和巴基斯坦人OR 1.9，P = 0.023；合并组OR 1.7，P = 0.003）。在英国白种人群体中，风险最高的是结节性RA，这是一种更严重的疾病亚型，与Fcγ受体IIIA - 158V等位基因纯合相关（OR 4.4，P = 0.004）。也有证据表明，在预测RA易感性方面，与RA相关的HLA - DRB1等位基因和至少一个Fcγ受体IIIA - 158V等位基因的存在之间存在相互作用（OR 5.5，P = 0.000）。
我们已经证明，Fcγ受体IIIA - 158V/F多态性是两个不同种族群体中RA的易感性和/或严重程度标志物。这一发现最终可能为RA和其他自身抗体/免疫复合物驱动的自身免疫性疾病的发病机制提供更多见解。
