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白细胞介素23受体变体与银屑病关节炎的关联。

Association of interleukin 23 receptor variants with psoriatic arthritis.

作者信息

Rahman Proton, Inman Robert D, Maksymowych Walter P, Reeve Jeff P, Peddle Lynette, Gladman Dafna D

机构信息

Department of Medicine, Memorial University, 154 Le Marchant Road, St. John's, NL, Canada, A1C 5B8.

出版信息

J Rheumatol. 2009 Jan;36(1):137-40. doi: 10.3899/jrheum.080458.

DOI:10.3899/jrheum.080458
PMID:19040306
Abstract

OBJECTIVE

A recent genome-wide pooling study noted a significant association of interleukin 23 receptor (IL-23R) and psoriasis. Overxpression of IL-23 has been detected in lesional psoriatic skin, and induces epidermal proliferation. Given the interplay between psoriasis and PsA, we examined the association of IL-23R variants in 2 independent Canadian Caucasian cohorts of patients with psoriatic arthritis (PsA).

METHODS

We examined 496 PsA probands and 476 controls. Cases and controls were genotyped for a panel of 11 single-nucleotide polymorphisms (SNP) in IL-23R. Allele and haplotype associations were calculated using WHAP software. P values for haplotype associations were calculated using a permutation test.

RESULTS

The 381Gln allele of the coding SNP Arg381Gln (rs11209026) was found to be protective in the Canadian population (p=0.004; corrected p=0.044). A 2-marker haplotype from SNP rs7530511 and rs11209026 was associated with PsA (p=0.011). All 3-marker sliding windows containing SNP rs11209026 were associated with PsA (p=0.02 for all 3 windows). The magnitude of effect of IL-23R association in PsA appears to be similar to that reported in uncomplicated psoriasis.

CONCLUSION

Significant associations between Arg381Gln SNP and haplotypes encoding this variant were noted in PsA. It remains to be determined what contribution of this association, if any, is specifically due to the inflammatory arthritis (PsA) rather than psoriasis.

摘要

目的

最近一项全基因组汇集研究指出,白细胞介素23受体(IL-23R)与银屑病之间存在显著关联。在银屑病皮损中已检测到IL-23的过度表达,且其可诱导表皮增殖。鉴于银屑病与银屑病关节炎(PsA)之间的相互作用,我们在两个独立的加拿大白种人银屑病关节炎患者队列中研究了IL-23R变异的关联性。

方法

我们检测了496例PsA先证者和476例对照。对病例和对照进行IL-23R中11个单核苷酸多态性(SNP)的基因分型。使用WHAP软件计算等位基因和单倍型关联性。单倍型关联性的P值通过置换检验计算。

结果

编码SNP Arg381Gln(rs11209026)的381Gln等位基因在加拿大人群中具有保护作用(p = 0.004;校正p = 0.044)。来自SNP rs7530511和rs11209026的一个双标记单倍型与PsA相关(p = 0.011)。包含SNP rs11209026的所有三标记滑动窗口均与PsA相关(所有三个窗口的p均为0.02)。IL-23R在PsA中的关联效应大小似乎与单纯银屑病中报道的相似。

结论

在PsA中发现Arg381Gln SNP与编码该变异的单倍型之间存在显著关联。这种关联的具体贡献(如果有的话)是由于炎性关节炎(PsA)而非银屑病,仍有待确定。

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