Filer Charlotte, Ho Pauline, Smith Rhodri L, Griffiths Christopher, Young Helen S, Worthington Jane, Bruce Ian N, Barton Anne
University of Manchester, Manchester, UK.
Arthritis Rheum. 2008 Dec;58(12):3705-9. doi: 10.1002/art.24128.
Recent reports have confirmed association of single-nucleotide polymorphisms (SNPs) mapping to the interleukin-23 receptor (IL-23R) and IL-12beta genes with psoriasis susceptibility. The aim of this study was to determine whether these variants are also associated with susceptibility to psoriatic arthritis (PsA).
Two IL23R SNPs (rs7530511 and rs11209026) and 2 IL12B SNPs (rs3212227 and rs6887695) were genotyped in DNA samples from 520 white patients with PsA and 2,260 control subjects, all of whom resided in the UK. For SNP rs3212227, data on a larger group of controls (n = 4,681) were publicly available; this information was used in the analysis. Genotype counts were compared between patients with PsA and population controls, using the trend test.
A haplotype comprising carriage of the common variants of both IL23R SNPs was associated with PsA susceptibility (adjusted P = 0.013 [1,000 permutations]). Both IL12B SNPs were independently associated with PsA susceptibility, and this association was strongest under a dominant model, with homozygosity for the common allele being more frequent in patients with PsA than in control subjects: for rs3212227, the odds ratio (OR) for carriage of AA versus other genotypes was 1.43 (95% confidence interval [95% CI] 1.17-1.76); for rs6887695, the OR for carriage of GG versus other genotypes was 1.43 (95% CI 1.18-1.74).
Variation within IL23R and IL12B is associated with susceptibility to both psoriasis and PsA. The effect sizes observed in patients with PsA appear to be smaller than those previously reported in patients with psoriasis, suggesting that both loci are primarily associated with psoriasis susceptibility. However, this does support the idea that the genetic etiology of the psoriasis present in patients with PsA has susceptibility loci in common with those observed in patients with uncomplicated psoriasis.
近期报告已证实，定位到白细胞介素23受体（IL-23R）和白细胞介素12β（IL-12β）基因的单核苷酸多态性（SNP）与银屑病易感性相关。本研究旨在确定这些变异是否也与银屑病关节炎（PsA）易感性相关。
对520例英国白人PsA患者及2260例对照者的DNA样本进行两个IL23R SNP（rs7530511和rs11209026）及两个IL12B SNP（rs3212227和rs6887695）的基因分型。对于SNP rs3212227，可公开获取更大一组对照者（n = 4681）的数据，该信息用于分析。采用趋势检验比较PsA患者与群体对照者的基因型计数。
包含两个IL23R SNP常见变异的单倍型与PsA易感性相关（校正P = 0.013[1000次置换]）。两个IL12B SNP均独立与PsA易感性相关，且这种关联在显性模型下最强，PsA患者中常见等位基因纯合子的频率高于对照者：对于rs3212227，携带AA与其他基因型相比的优势比（OR）为1.43（95%置信区间[95%CI]1.17 - 1.76）；对于rs6887695，携带GG与其他基因型相比的OR为1.43（95%CI 1.18 - 1.74）。
IL23R和IL12B内的变异与银屑病和PsA的易感性均相关。在PsA患者中观察到的效应大小似乎小于先前在银屑病患者中报告的效应大小，这表明这两个基因座主要与银屑病易感性相关。然而，这确实支持了PsA患者中存在的银屑病的遗传病因与单纯银屑病患者中观察到的有共同易感基因座这一观点。
