Leeds Institute of Genetics, Health and Therapeutics (LIGHT), University of Leeds, UK.
BMC Med. 2010 Jan 13;8:5. doi: 10.1186/1741-7015-8-5.
Inflammatory cytokines play a crucial role in coronary artery disease (CAD). We investigated the association between 48 coding and three non-coding single nucleotide polymorphisms (SNPs) from 35 inflammatory genes and the development of CAD, using a large discordant sibship collection (2699 individuals in 891 families).
Family-based association tests (FBAT) and conditional logistic regression (CLR) were applied to single SNPs and haplotypes and, in CLR, traditional risk factors of CAD were adjusted for.
An association was observed between CAD and a common three-locus haplotype in the interleukin one (IL-1) cluster with P = 0.006 in all CAD cases, P = 0.01 in myocardial infarction (MI) cases and P = 0.0002 in young onset CAD cases (<50 years). The estimated odds ratio (OR) per copy of this haplotype is 1.21 (95% confidence interval [95CI] = 1.04 - 1.40) for CAD; 1.30 (95CI = 1.09 - 1.56) for MI and 1.50 (95CI = 1.22 - 1.86) for young onset CAD. When sex, smoking, hypertension and hypercholesterolaemia were adjusted for, the haplotype effect remained nominally significant (P = 0.05) in young onset CAD cases, more so (P = 0.002) when hypercholesterolaemia was excluded. As many as 82% of individuals affected by CAD had hypercholesterolaemia compared to only 29% of those unaffected, making the two phenotypes difficult to separate.
Despite the multiple hypotheses tested, the robustness of family design to population confoundings and the consistency with previous findings increase the likelihood of true association. Further investigation using larger data sets is needed in order for this to be confirmed. See the related commentary by Keavney: http://www.biomedcentral.com/1741-7015/8/6.
炎症细胞因子在冠心病（CAD）中起着至关重要的作用。我们使用一个大型的不相关的同胞集合（2699 个人在 891 个家庭），研究了 35 个炎症基因的 48 个编码和 3 个非编码单核苷酸多态性（SNP）与 CAD 发展之间的关联。
采用基于家庭的关联检验（FBAT）和条件逻辑回归（CLR）分析单个 SNP 和单倍型，并在 CLR 中调整 CAD 的传统危险因素。
在所有 CAD 病例中，白细胞介素 1（IL-1）簇中一个常见的三核苷酸单倍型与 CAD 之间存在关联，P = 0.006；在心肌梗死（MI）病例中，P = 0.01；在年轻发病 CAD 病例（<50 岁）中，P = 0.0002。该单倍型的估计每拷贝的优势比（OR）为 1.21（95%置信区间[95CI] = 1.04-1.40），用于 CAD；1.30（95CI = 1.09-1.56）用于 MI；1.50（95CI = 1.22-1.86）用于年轻发病 CAD。当调整性别、吸烟、高血压和高胆固醇血症等因素后，该单倍型效应在年轻发病 CAD 病例中仍具有名义显著性（P = 0.05），当排除高胆固醇血症时更为显著（P = 0.002）。患有 CAD 的个体中有 82%的人伴有高胆固醇血症，而未患有 CAD 的个体中只有 29%的人伴有高胆固醇血症，这使得这两种表型难以区分。
尽管进行了多次假设检验，但家庭设计对人群混杂因素的稳健性以及与先前发现的一致性增加了真正关联的可能性。需要使用更大的数据集进行进一步研究，以确认这一点。请参阅相关评论文章：http://www.biomedcentral.com/1741-7015/8/6。
