Centre for Prognosis Studies in Rheumatic Diseases, Toronto Western Hospital, Toronto, Canada.
Ann Rheum Dis. 2012 Jan;71(1):50-5. doi: 10.1136/ard.2011.155044. Epub 2011 Sep 6.
Aim Genes that differentiate patients with psoriatic arthritis (PsA) from those with cutaneous psoriasis (PsC) may serve as markers for the development of PsA in patients with psoriasis. The authors aimed to identify human leucocyte antigen (HLA) alleles that are associated with the development of PsA in patients with psoriasis.
712 adult patients with PsA, 335 adult patients with PsC and 713 healthy controls were genotyped for HLA-A, HLA-B, HLA-C, HLA-DR and HLA-DQ alleles. Differences in allelic distributions for each of the HLA loci were compared using a likelihood ratio test. Logistic regression analysis of multiple loci was performed to account for linkage disequilibrium. Haplotype information was inferred using the expectation-maximisation algorithm (given HLA-C and HLA-B genotypes) and analysed similarly.
The following HLA alleles were found to be significantly associated with patients with PsA compared to patients with PsC in multivariate regression analysis: B08 (OR 1.61, p=0.009), B27 (OR 5.17, p<0.0001), B38 (OR 1.65, p=0.026) and C06 (OR 0.58, p=0.0002). HLA-B27, HLA-B38 and HLA-C06 frequencies were also significantly higher in patients with PsA than in healthy controls (B27: OR 3.05, p<0.0001; B38: OR 5.9, p<0.0001; HLA-C06: OR 1.71, p<0.0001). The following haplotypes were independently associated with PsA compared to PsC: HLA-B18-C07 (OR 10.1, p=0.004), HLA-B27-C01 (OR 41.1, p<0.0001), HLA-B27-C02 (OR 19.9, p<0.0001), HLA-B38-C12 (OR 2.9, p=0.01), HLA-B08-C07 (OR 2.6, p=0.004) and HLA-B57-C06 (OR 0.5, p=0.03).
Certain HLA-B and HLA-C alleles confer susceptibility to PsA among patients with psoriasis and may be used to identify patients with PsC who may develop PsA.
区分银屑病关节炎(PsA)和银屑病(PsC)患者的基因可能成为预测银屑病患者发生 PsA 的标志物。本研究旨在鉴定与银屑病患者发生 PsA 相关的人类白细胞抗原(HLA)等位基因。
对 712 例成年 PsA 患者、335 例成年 PsC 患者和 713 名健康对照者进行 HLA-A、HLA-B、HLA-C、HLA-DR 和 HLA-DQ 等位基因分型。采用似然比检验比较各 HLA 位点等位基因分布的差异。采用多基因连锁不平衡分析对多个位点进行逻辑回归分析。采用期望最大化算法推断单体型信息(基于 HLA-C 和 HLA-B 基因型),并进行类似分析。
多变量回归分析显示,与 PsC 患者相比,以下 HLA 等位基因与 PsA 患者显著相关:B08(OR 1.61,p=0.009)、B27(OR 5.17,p<0.0001)、B38(OR 1.65,p=0.026)和 C06(OR 0.58,p=0.0002)。HLA-B27、HLA-B38 和 HLA-C06 频率在 PsA 患者中也显著高于健康对照组(B27:OR 3.05,p<0.0001;B38:OR 5.9,p<0.0001;HLA-C06:OR 1.71,p<0.0001)。与 PsC 相比,以下单体型与 PsA 独立相关:HLA-B18-C07(OR 10.1,p=0.004)、HLA-B27-C01(OR 41.1,p<0.0001)、HLA-B27-C02(OR 19.9,p<0.0001)、HLA-B38-C12(OR 2.9,p=0.01)、HLA-B08-C07(OR 2.6,p=0.004)和 HLA-B57-C06(OR 0.5,p=0.03)。
某些 HLA-B 和 HLA-C 等位基因可使银屑病患者易患 PsA,并且可能用于识别可能发生 PsA 的 PsC 患者。