Gallagher P M, Lowe G, Fitzgerald T, Bella A, Greene C M, McElvaney N G, O'Neill S J
Division of Respiratory Research, Department of Medicine, RCSI Education and Research Centre, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland.
Thorax. 2003 Feb;58(2):154-6. doi: 10.1136/thorax.58.2.154.
The influence of genetic polymorphisms of interleukin (IL)-10, tumour necrosis factor (TNF)-alpha, and IL-6 gene promoters on severity of systemic inflammatory response syndrome (SIRS) associated with community acquired pneumonia (CAP) was studied.
Using PCR-RFLP analysis we analysed a -1082G/A single nucleotide polymorphism (SNP) of the anti-inflammatory IL-10 gene, a -308G/A SNP of the pro-inflammatory TNF-alpha gene and a -174G/C SNP of the IL-6 gene. Illness severity was stratified according to SIRS score, calculated by presence of up to four physiological indices: temperature, white blood cell count, heart rate and respiratory rate (non-SIRS, SIRS 2, SIRS 3, and SIRS 4).
A statistically significant stepwise increase in frequency of the IL-10 G allele, associated with higher expression of the gene, was observed in patients with increasing severity of illness from non-SIRS (n=19) to SIRS 2 (n=17), SIRS 3 (n=33) and SIRS 4 (n=24). This was primarily due to a higher frequency of the GG genotype with increasing severity from non-SIRS through to SIRS 4. IL-10 G allele frequency was also increased in patients who died as a result of CAP (n=11) compared with CAP survivors (n=82) (p=0.01). No association was seen between the TNF-alpha -308G/A and IL-6 -174G/C SNPs and disease. Additionally, no interaction between all three SNP genotypes and disease severity was observed.
A polymorphism affecting IL-10 expression may influence the severity of illness in patients with CAP.
研究白细胞介素(IL)-10、肿瘤坏死因子(TNF)-α和IL-6基因启动子的基因多态性对社区获得性肺炎(CAP)相关全身炎症反应综合征(SIRS)严重程度的影响。
我们采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析方法,分析抗炎性IL-10基因的-1082G/A单核苷酸多态性(SNP)、促炎性TNF-α基因的-308G/A SNP以及IL-6基因的-174G/C SNP。根据SIRS评分对疾病严重程度进行分层,SIRS评分通过以下四个生理指标计算得出:体温、白细胞计数、心率和呼吸频率(非SIRS、SIRS 2、SIRS 3和SIRS 4)。
随着疾病严重程度从非SIRS(n = 19)增加到SIRS 2(n = 17)、SIRS 3(n = 33)和SIRS 4(n = 24),观察到与基因高表达相关的IL-10 G等位基因频率呈统计学显著的逐步增加。这主要是由于从非SIRS到SIRS 4严重程度增加时GG基因型频率更高。与CAP幸存者(n = 82)相比,因CAP死亡的患者(n = 11)中IL-10 G等位基因频率也增加(p = 0.01)。未观察到TNF-α -308G/A和IL-6 -174G/C SNPs与疾病之间存在关联。此外,未观察到所有三种SNP基因型与疾病严重程度之间存在相互作用。
影响IL-10表达的多态性可能影响CAP患者的疾病严重程度。