白细胞介素-1基因簇多态性与吸烟所致慢性阻塞性肺疾病中C反应蛋白浓度及肺功能下降的相关性
Associations of interleukin-1 gene cluster polymorphisms with C-reactive protein concentration and lung function decline in smoking-induced chronic obstructive pulmonary disease.
作者信息
Wang Yu, Shumansky Karey, Sin Don D, Man S F Paul, Akhabir Loubna, Connett John E, Anthonisen Nicholas R, Paré Peter D, Sandford Andrew J, He Jian-Qing
机构信息
Department of Respiratory and Critical Medicine, West China Hospital of Sichuan University Chengdu, Sichuan Province, China.
Centre for Heart Lung Innovation, University of British Columbia and St. Paul's Hospital Vancouver, BC, Canada.
出版信息
Int J Clin Exp Pathol. 2015 Oct 1;8(10):13125-35. eCollection 2015.
OBJECTIVE
We reported association of haplotypes formed by IL-1b (IL1B)-511C/T (rs16944) and a variable number of tandem repeats (rs2234663) in intron 3 of IL-1 receptor antagonist (IL1RN) with rate of lung function decline in smoking-induced COPD. The aim of current study was to further investigate this association.
METHODS
We genotyped an additional 19 polymorphisms in IL1 cluster (including IL1A, IL1B and IL1RN) in non-Hispanic whites who had the fastest (n = 268) and the slowest (n = 292) decline of FEV1% predicted in the same study. We also analyzed the association of all 21 polymorphisms with serum CRP levels.
RESULTS
None of 21 polymorphisms showed significant association with rate of decline of lung function or CRP levels after adjusting for multiple comparisons. Before adjusting for multiple comparisons, only IL1RN_19327 (rs315949) showed significant association with lung function decline (P = 0.03, additive model). The frequencies of genotypes containing the IL1RN_19327A allele were 71.9% and 62.2%, respectively in the fast and slow decline groups (P = 0.02, odds ratio = 1.6, 95% confidence interval = 1.1-2.3); the IL1B_5200 (rs1143633) and rs2234663 in IL1RN were associated with serum CRP levels (P=0.04 and 0.03, respectively).
CONCLUSIONS
No single marker was significantly associated with either rate of lung function decline or serum CRP levels.
目的
我们报告了白细胞介素-1β（IL-1b，即IL1B）-511C/T（rs16944）以及白细胞介素-1受体拮抗剂（IL-1ra，即IL1RN）第3内含子中可变串联重复序列（rs2234663）所形成的单倍型与吸烟所致慢性阻塞性肺疾病（COPD）患者肺功能下降速率之间的关联。本研究的目的是进一步探究这种关联。
方法
我们对同一研究中预测第一秒用力呼气容积（FEV1）下降最快（n = 268）和最慢（n = 292）的非西班牙裔白人的IL1基因簇（包括IL1A、IL1B和IL1RN）中的另外19个多态性位点进行了基因分型。我们还分析了所有这21个多态性位点与血清C反应蛋白（CRP）水平之间的关联。
结果
在进行多重比较校正后，21个多态性位点中没有一个与肺功能下降速率或CRP水平存在显著关联。在进行多重比较校正前，只有IL1RN_19327（rs315949）与肺功能下降存在显著关联（P = 0.03，加性模型）。在下降快和下降慢的两组中，含有IL1RN_19327A等位基因的基因型频率分别为71.9%和62.2%（P = 0.02，比值比 = 1.6，95%置信区间 = 1.1 - 2.3）；IL1RN中的IL1B_5200（rs1143633）和rs2234663与血清CRP水平相关（分别为P = 0.04和P = 0.03）。
结论
没有单一标记物与肺功能下降速率或血清CRP水平存在显著关联。
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