白细胞介素-1B及其受体拮抗剂基因多态性与韩国人群慢性阻塞性肺疾病风险：一项病例对照研究。
Polymorphisms in interleukin-1B and its receptor antagonist genes and the risk of chronic obstructive pulmonary disease in a Korean population: a case-control study.
作者信息
Lee Jong Myung, Kang Yeh Rim, Park Sun Ha, Cha Sung Ick, Kim Jong Sik, Kang Hyo Kyung, Lee Won Kee, Kim Min Jung, Kim Chang Ho, Kim Nung Soo, Jung Tae Hoon, Park Jae Yong
机构信息
Department of Internal Medicine, Kyungpook National University Hospital, Samduk 2Ga 50, Daegu, 700-412, South Korea; Brain Korea 21, School of Medicine, Kyungpook National University, Dong In 2Ga 101, Daegu, South Korea.
出版信息
Respir Med. 2008 Sep;102(9):1311-20. doi: 10.1016/j.rmed.2008.03.026. Epub 2008 Jun 24.
BACKGROUND
Although several studies have evaluated the association between interleukin-1B (IL1B) polymorphisms and the risk of chronic obstructive pulmonary disease (COPD), most of these studies have focused on -511C-->T and -31T-->C polymorphisms, and the results of these studies have been inconsistent. This study was conducted to investigate the association between four potentially functional polymorphisms of the IL1B gene (-3737C-->T, -1464G-->C, -511C-->T, and -31T-->C) and the risk of COPD. In addition, we examined a potential interaction of the IL1B polymorphisms with the VNTR polymorphism of the IL-1 receptor antagonist (IL1RN) gene in determining the risk of COPD.
METHODS
The IL1B and IL1RN genotypes were determined in 311 COPD patients and 386 healthy controls.
RESULTS
Individuals with at least one variant allele of the -511C-->T and -31T-->C polymorphisms were at a significantly increased risk for COPD when compared to carriers with each homozygous wild-type allele [adjusted odds ratio (OR) 1.53, 95% confidence interval (CI) 1.03-2.26, P=0.03; and adjusted OR 1.50, 95% CI 1.02-2.24, P=0.04, respectively]. When the COPD cases were stratified according to disease severity, the presence of at least one -511T and -31C alleles was significantly associated with severe COPD (adjusted OR 2.80, 95% CI 1.47-5.33, P=0.002; and adjusted OR 2.33, 95% CI 1.24-4.40, P=0.01, respectively), however, there was no significant association between the -511C-->T and -31T-->C genotypes and mild-to-moderate COPD. In addition, individuals carrying at least one IL1RN2 allele were at a significantly lower risk for COPD compared to subjects carrying no IL1RN2 allele (adjusted OR 0.51, 95% CI 0.26-0.98, P=0.04). In haplotype/diplotype analyses, individuals with one or two copies of the IL1B CCTC haplotype that carried the risk allele at all of the -3737C-->T, -1464G-->C, -511C-->T, and -31T-->C loci, were at a significantly increased risk of severe COPD when compared with subjects with zero copy of the CCTC haplotype (adjusted OR 1.96, 95% CI 1.16-3.29, P=0.01).
CONCLUSION
These findings suggest that polymorphisms in the IL1B and IL1RN genes might be useful markers for determining genetic susceptibility to COPD in a Korean population.
背景
尽管多项研究评估了白细胞介素-1β（IL1B）基因多态性与慢性阻塞性肺疾病（COPD）风险之间的关联，但这些研究大多集中在-511C→T和-31T→C多态性上，且研究结果并不一致。本研究旨在调查IL1B基因的四个潜在功能性多态性（-3737C→T、-1464G→C、-511C→T和-31T→C）与COPD风险之间的关联。此外，我们还研究了IL1B基因多态性与白细胞介素-1受体拮抗剂（IL1RN）基因可变数目串联重复序列（VNTR）多态性在决定COPD风险方面的潜在相互作用。
方法
对311例COPD患者和386例健康对照者进行IL1B和IL1RN基因分型。
结果
与每个纯合野生型等位基因携带者相比，-511C→T和-31T→C多态性中至少有一个变异等位基因的个体患COPD的风险显著增加[调整后的优势比（OR）分别为1.53，95%置信区间（CI）为1.03 - 2.26，P = 0.03；调整后的OR为1.50，95% CI为1.02 - 2.24，P = 0.04]。当根据疾病严重程度对COPD病例进行分层时，至少存在一个-511T和-31C等位基因与重度COPD显著相关（调整后的OR分别为2.80，95% CI为1.47 - 5.33，P = 0.002；调整后的OR为2.33，95% CI为1.24 - 4.40，P = 0.01），然而，-511C→T和-31T→C基因型与轻至中度COPD之间无显著关联。此外，与未携带IL1RN2等位基因的受试者相比，携带至少一个IL1RN2等位基因的个体患COPD的风险显著降低（调整后的OR为0.51，95% CI为0.26 - 0.98，P = 0.04）。在单倍型/双倍型分析中，与CCTC单倍型零拷贝的受试者相比，在-3737C→T、-1464G→C、-511C→T和-31T→C位点均携带风险等位基因的一个或两个拷贝的IL1B CCTC单倍型个体患重度COPD的风险显著增加（调整后的OR为1.96，95% CI为1.16 - 3.29，P = 0.01）。
结论
这些发现表明，IL1B和IL1RN基因中的多态性可能是确定韩国人群COPD遗传易感性的有用标志物。
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