Associations of IL6 polymorphisms with lung function decline and COPD.
Associations of IL6 polymorphisms with lung function decline and COPD.
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DOI：
10.1136/thx.2008.111278
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发表时间：
2009-08
期刊：
影响因子：
10
通讯作者：
Sandford AJ
中科院分区：
文献类型：
--
作者：
He JQ;Foreman MG;Shumansky K;Zhang X;Akhabir L;Sin DD;Man SF;DeMeo DL;Litonjua AA;Silverman EK;Connett JE;Anthonisen NR;Wise RA;Paré PD;Sandford AJ
白细胞介素-6 （Interleukin-6, IL6）是一种多效性的促炎和免疫调节细胞因子，可能在COPD的发病机制中起重要作用。在IL6的启动子区域有一个功能性的单核苷酸多态性（SNP），−174G/C。我们假设IL6 snp影响吸烟者肺功能受损和COPD的易感性。基于5年内一秒钟用力呼气量（FEV1）下降率的表型和LHS开始时的基线FEV1，在来自肺健康研究（LHS）的两个巢式病例对照样本中对IL6中的7个和5个snp进行了基因分型。测定所有受试者的血清IL6浓度。对来自国家肺气肿治疗试验（NETT）的389例COPD患者和来自规范衰老研究（NAS）的420例对照进行了部分重叠的9个IL6 snp组基因分型。在LHS中，3个IL6 snp与FEV1下降相关（在加性模型中为0.023≤P≤0.041）。其中IL6_−174C等位基因与肺功能快速下降相关。在基于基因型的分析中，这种关联更为显著（P = 0.006）。在net - nas研究中，IL6_−174G/C和其他4个与IL6_−174G/C连锁不平衡的IL6 snp与COPD易感性相关（加性遗传模型中0.01≤P≤0.04）。我们的研究结果表明，IL6_−174G/C SNP与吸烟者FEV1快速下降和COPD易感性相关。
Interleukin-6 (IL6) is a pleiotropic pro-inflammatory and immunomodulatory cytokine which likely plays an important role in the pathogenesis of COPD. There is a functional single nucleotide polymorphism (SNP), −174G/C, in the promoter region of IL6. We hypothesized that IL6 SNPs influence susceptibility for impaired lung function and COPD in smokers. Seven and 5 SNPs in IL6 were genotyped in two nested case-control samples derived from the Lung Health Study (LHS) based on phenotypes of rate of decline of forced expiratory volume in one second (FEV1) over 5 years and baseline FEV1 at the beginning of the LHS. Serum IL6 concentrations were measured for all subjects. A partially overlapping panel of 9 IL6 SNPs was genotyped in 389 COPD cases from the National Emphysema Treatment Trial (NETT) and 420 controls from the Normative Aging Study (NAS). In the LHS, three IL6 SNPs were associated with FEV1 decline (0.023 ≤ P ≤ 0.041 in additive models). Among them the IL6_−174C allele was associated with rapid decline of lung function. The association was more significant in a genotype-based analysis (P = 0.006). In the NETT-NAS study, IL6_−174G/C and four other IL6 SNPs, all of which are in linkage disequilibrium with IL6_−174G/C, were associated with susceptibility to COPD (0.01 ≤ P ≤ 0.04 in additive genetic models). Our results suggest that the IL6_−174G/C SNP is associated with rapid decline of FEV1 and susceptibility to COPD in smokers.
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DOI：
10.1164/ajrccm.163.2.2006158
发表时间：
2001-02-01
影响因子：
24.7
作者：
Sandford, AJ;Chagani, T;Paré, PD
通讯作者：
Paré, PD
影响因子：
9.8
作者：
Ardlie, KG;Lunetta, KL;Seielstad, M
通讯作者：
Seielstad, M
影响因子：
5.3
作者：
He, JQ;Burkett, K;Sandford, AJ
通讯作者：
Sandford, AJ
影响因子：
11.4
作者：
MAJELLO, B;ARCONE, R;CILIBERTO, G
通讯作者：
CILIBERTO, G
影响因子：
24.3
作者：
He, J-Q.;Shumansky, K.;Sandford, A. J.
通讯作者：
Sandford, A. J.