Interferon gamma polymorphisms and their interaction with smoking are associated with lung function
Interferon gamma polymorphisms and their interaction with smoking are associated with lung function
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DOI：
10.1007/s00439-006-0143-z
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发表时间：
2006-05-01
期刊：
影响因子：
5.3
通讯作者：
Sandford, AJ
中科院分区：
文献类型：
--
作者：
He, JQ;Burkett, K;Sandford, AJ
遗传和环境决定因素之间的相互作用可能在慢性阻塞性肺病的发病机制中很重要。我们假设干扰素γ（IFNG）单核苷酸多态性（SNP）及其与吸烟的相互作用与吸烟者肺功能下降的速度或水平相关。我们研究了585名非西班牙裔白人（NHW）IFNG中的4个SNP，这些人的FEV1%预测值下降最快（n =280）或最慢（n=305），这些人选自NHLBI肺健康研究中随访5年的连续吸烟者。我们还研究了1061名在LHS开始时基线肺功能最低（n=530）或最高（n=531）的NHW。两个SNP与肺功能的基线水平相关，显性模型中+2197 T/C的p值为0.008，隐性模型中+5171 A/G的p值为0.002。然而，在调整混杂因素后，只有+5171A/G仍然具有显著性（隐性模型p=0.001）。此外，对于基线肺功能，+5171 A/G（GG vs.GA + AA）存在显著的基因型和吸烟相互作用，p=0.006。当比较GG个体与AG + AA个体的低肺功能时，调整后的比值比随着包年的增加而显著降低。在下降率研究中没有发现相关性。IFNG基因型与基线肺功能之间存在相关性，吸烟改变了这种相关性。
Interactions between genetic and environmental determinants are likely to be important in the pathogenesis of chronic obstructive pulmonary disease. We hypothesized that interferon gamma (IFNG) single nucleotide polymorphisms (SNPs) and their interaction with smoking are associated with the rate of decline or level of lung function in smokers. We studied four SNPs in IFNG in 585 non-Hispanic whites (NHW) who had the fastest (n =280) or the slowest (n=305) decline of FEV1% predicted selected from among continuous smokers followed for 5 years in the NHLBI Lung Health Study. We also studied 1061 NHW with the lowest (n=530) or the highest (n=531) baseline lung function at the beginning of the LHS. Two SNPs were associated with baseline levels of lung function and the p values were 0.008 for +2197T/C in a dominant model and 0.002 for +5171A/G in a recessive model. However, after adjusting for confounding factors, only +5171A/G was still significant (p=0.001 for the recessive model). In addition, there was a significant genotype and smoking interaction with p=0.006 for the +5171A/G (GG vs.GA + AA) for the baseline lung function. When comparing individuals with GG versus individuals with AG + AA for low lung function, the adjusted odds ratios decreased significantly as pack-years increased. No association was found in the rate of decline study. There was an association between IFNG genotype and baseline of lung function and this association was modified by cigarette smoking.