Balding J, Healy C M, Livingstone W J, White B, Mynett-Johnson L, Cafferkey M, Smith O P
Department of Genetics, Trinity College, Dublin, Ireland.
Genes Immun. 2003 Dec;4(8):533-40. doi: 10.1038/sj.gene.6364020.
Patients with meningococcal disease have increased plasma levels of proinflammatory cytokines IL-6, IL-1beta, and TNF-alpha, with higher levels associated with fatal outcome. This study investigated whether polymorphisms in genes encoding these cytokines, and in those encoding anti-inflammatory IL-10 and IL-1Ra, are associated with the outcome in patients with meningococcal disease. Seven polymorphisms were genotyped in 183 meningococcal disease patients and 389 controls. The IL-6 -174 G/G and IL-10 -1082 A/A genotypes were more frequent in nonsurvivors compared with survivors (P=0.023 IL-6, 0.25 IL-10), and in patients with severe disease compared to those with mild disease (P=0.037 IL-6, 0.0078 IL-10). An association was also found between meningococcal disease and the IL-1RN VNTR polymorphism, but no association was observed with the LTA +252, TNF -308, IL-10 -592, or IL-1B +3953 polymorphisms. We conclude that genetic variability in the IL-6, IL-10, and IL-1RN genes is associated with a poor outcome in meningococcal disease.
患有脑膜炎球菌病的患者血浆中促炎细胞因子白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)和肿瘤坏死因子-α(TNF-α)水平升高,较高水平与致命结局相关。本研究调查了编码这些细胞因子的基因以及编码抗炎性白细胞介素-10(IL-10)和白细胞介素-1受体拮抗剂(IL-1Ra)的基因中的多态性是否与脑膜炎球菌病患者的结局相关。对183例脑膜炎球菌病患者和389例对照进行了7种多态性的基因分型。与幸存者相比,非幸存者中IL-6 -174 G/G和IL-10 -1082 A/A基因型更为常见(IL-6,P=0.023;IL-10,P=0.25),与轻症患者相比,重症患者中更为常见(IL-6,P=0.037;IL-10,P=0.0078)。还发现脑膜炎球菌病与IL-1RN可变数目串联重复序列(VNTR)多态性之间存在关联,但未观察到与LTA +252、TNF -308、IL-10 -592或IL-1B +3953多态性之间存在关联。我们得出结论,IL-6、IL-10和IL-1RN基因的遗传变异性与脑膜炎球菌病的不良结局相关。