Killer-cell immunoglobulin-like receptor gene polymorphisms and susceptibility to psoriatic arthritis
Killer-cell immunoglobulin-like receptor gene polymorphisms and susceptibility to psoriatic arthritis
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DOI：
10.1093/rheumatology/ket296
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发表时间：
2014-02-01
期刊：
影响因子：
5.5
通讯作者：
Gladman, Dafna D.
中科院分区：
文献类型：
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作者：
Chandran, Vinod;Bull, Shelley B.;Gladman, Dafna D.
目标。我们进行了病例对照研究，以确定KIR2D和KIR3D基因多态性与PSA的关联及其与HLA等位基因的交互作用。共对678例PSA患者和688例健康对照进行了研究。病例组和对照组个体KIR基因多态频率的差异通过渐近X(2)检验和Fisher‘s精确检验进行显著性检验。Cochran-Armitage趋势检验评估联合基因(HLAKIR和HLAKIR)对PSA易感性增加的趋势。多基因Logistic回归分析确定独立的关联和交互作用。在单变量分析中，KIR2DL2和KIR2DS2基因多态性与PSA显著相关。多因素分析显示，只有KIR2DS2与健康对照组PSA相关[优势比(OR)1.25，95%可信区间1.01，1.54，P=0.044]。人类白细胞抗原C组2等位基因的存在与前列腺特异性抗原的发病风险相关(趋势检验P=0.006)。当KIR2DS2存在相应抑制性KIRS的人类白细胞抗原-C配体(C组1)时，发生PSA的风险更高，与不存在KIR2DS2时相比，当KIR2DS2存在而没有同源抑制物KIRS的HLAC配体时，PSA的风险最高(趋势检验P=0.027)。具有高细胞表面表达的人类白细胞抗原-C等位基因的存在也与PSA的高风险相关(趋势检验P<；0.001)。HLABbw4和HLABbw4 80ile等位基因组与PSA风险增加相关(趋势检验P<；两种分析均为0.0001)。本研究证实了KIR2DS基因，尤其是KIR2DS2基因与PSA的相关性。
Objectives. We conducted a case-control study to determine the association between KIR2D and KIR3D gene polymorphisms and their interaction with HLA alleles in PsA.Methods. A total of 678 subjects with PsA and 688 healthy controls were studied. Differences between cases and controls in the frequency of individual KIR polymorphisms were tested for significance by an asymptotic chi(2) test and Fisher's exact test. Trends for increasing susceptibility to PsA from combined genotypes (HLA-KIR and HLA) were evaluated by the Cochran-Armitage trend test. Multigene logistic regression analysis was conducted to identify independent associations and interactions.Results. In univariate analyses, KIR2DL2 and KIR2DS2 polymorphisms were significantly associated with PsA. Only KIR2DS2 was associated with PsA compared with healthy controls in multivariate analysis [odds ratio (OR) 1.25, 95% CI 1.01, 1.54, P = 0.044]. The presence of HLA-C group 2 alleles was associated with a higher risk of PsA (trend test P = 0.006). The risk of PsA is higher when KIR2DS2 is present with the HLA-C ligands (C group 1) for the corresponding inhibitory KIRs, and is highest when KIR2DS2 is present in the absence of HLA-C ligands for homologous inhibitor KIRs, compared with the state when KIR2DS2 is absent (trend test P = 0.027). The presence of HLA-C alleles that have high cell surface expression was also associated with a higher risk of PsA (trend test P < 0.001). HLA-B Bw4 and HLA-B Bw4 80ile allele groups were associated with a higher PsA risk (trend test P < 0.0001 for both analyses).Conclusion. This study confirms the association of the KIR2DS gene, especially KIR2DS2, with PsA.