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
Hospital Universitario Virgen del Rocío, Seville, Spain.
Respir Med. 2009 Mar;103(3):427-33. doi: 10.1016/j.rmed.2008.09.014. Epub 2008 Nov 29.
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.
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.
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.
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.
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。
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。
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。
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。