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环氧化酶-2基因多态性使结节病易感性增加,但与预后无关。

Cyclooxygenase-2 polymorphisms confer susceptibility to sarcoidosis but are not related to prognosis.

作者信息

Lopez-Campos José Luis, Rodriguez-Rodriguez David, Rodriguez-Becerra Eulogio, Alfageme Michavila Inmaculada, Guerra Jose Fernandez, Hernandez Francisco Javier García, Casanova Alvaro, Fernández de Córdoba Gamero Javier, Romero-Ortiz Ana, Arellano-Orden Elena, Montes-Worboys Ana

机构信息

Hospital Universitario Virgen del Rocío, Seville, Spain.

出版信息

Respir Med. 2009 Mar;103(3):427-33. doi: 10.1016/j.rmed.2008.09.014. Epub 2008 Nov 29.

Abstract

BACKGROUND

The aim of this multicenter study was to investigate the relationship between single nucleotide polymorphisms (SNPs) of the cyclooxygenase-2 (COX2) gene and susceptibility to sarcoidosis, as well as the relation between these SNPs and the evolution of the disease.

MATERIAL AND METHODS

This multicenter investigation involved seven hospitals in Spain. We used a case-control design followed by a prospective follow-up study. Sarcoid patients were recruited from the participating institutions during outpatient routine visits. Age- and gender-matched control subjects were recruited mainly from among outpatients attending the participating hospitals. Four SNPs in the COX2 gene (COX2.5909 T > G, COX2.8473 T > C, COX2.926 G > C, and COX2.3050 G > C) were genotyped using fluorescent hybridization probes among 131 patients with sarcoidosis (63 males; mean age: 47 +/- 15 years) and 157 healthy controls (83 males; mean age: 50 +/- 16 years). We employed a binomial multiple logistic regression analysis to test the association between the selected SNPs and disease susceptibility. The clinical, functional and radiological prognosis of the sarcoidosis patients was determined after a mean follow-up of 37.4 +/- 30.4 months.

RESULTS

Carriers of the homozygous CC genotype of the COX2.8473 T > C polymorphism had a higher risk of sarcoidosis compared with TT carriers (OR: 3.08; 95% CI: 1.2-7.7; p = 0.035). 84% of patients achieved improvement or complete remission at follow-up. No association between the investigated SNPs and prognosis was seen.

CONCLUSIONS

Our data suggest that the homozygous CC genotype of the COX2.8473 T > C polymorphism may be associated with sarcoidosis susceptibility. No significant association with prognosis was detected.

摘要

背景

这项多中心研究的目的是调查环氧化酶-2(COX2)基因的单核苷酸多态性(SNP)与结节病易感性之间的关系,以及这些SNP与疾病进展之间的关系。

材料与方法

这项多中心调查涉及西班牙的七家医院。我们采用病例对照设计,随后进行前瞻性随访研究。结节病患者在门诊常规就诊期间从参与机构招募。年龄和性别匹配的对照对象主要从参与医院的门诊患者中招募。使用荧光杂交探针在131例结节病患者(63例男性;平均年龄:47±15岁)和157例健康对照者(83例男性;平均年龄:50±16岁)中对COX2基因的四个SNP(COX2.5909 T>G、COX2.8473 T>C、COX2.926 G>C和COX2.3050 G>C)进行基因分型。我们采用二项式多元逻辑回归分析来检验所选SNP与疾病易感性之间的关联。在平均随访37.4±30.4个月后,确定结节病患者的临床、功能和放射学预后。

结果

与TT携带者相比,COX2.8473 T>C多态性的纯合CC基因型携带者患结节病的风险更高(比值比:3.08;95%可信区间:1.2 - 7.7;p = 0.035)。84%的患者在随访时病情改善或完全缓解。未发现所研究的SNP与预后之间存在关联。

结论

我们的数据表明,COX2.8473 T>C多态性的纯合CC基因型可能与结节病易感性相关。未检测到与预后的显著关联。

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