Women and Infants Hospital/Alpert Medical School of Brown University, Providence, Rhode Island 02903, USA.
JAMA. 2010 Feb 17;303(7):648-56. doi: 10.1001/jama.2010.118.
Associations between chromosome 9p21 single-nucleotide polymorphisms (SNPs) and heart disease have been reported and replicated. If testing improves risk assessments using traditional factors, it may provide opportunities to improve public health.
To perform a targeted systematic review of published literature for effect size, heterogeneity, publication bias, and strength of evidence and to consider whether testing might provide clinical utility.
Electronic search via HuGE Navigator through January 2009 and review of reference lists from included articles.
English-language articles that tested for 9p21 SNPs with coronary heart/artery disease or myocardial infarction as primary outcomes. Included articles also provided race, numbers of participants, and data to compute an odds ratio (OR). Articles were excluded if reporting only intermediate outcomes (eg, atherosclerosis) or if all participants had existing disease. Twenty-five articles were initially identified and 16 were included. A follow-up search identified 6 additional articles.
Independent extraction was performed by 2 reviewers and consensus was reached. Credibility of evidence was assessed using published Venice criteria.
Forty-seven distinct data sets from the 22 articles were analyzed, including 35 872 cases and 95 837 controls. The summary OR for heart disease among individuals with 2 vs 1 at-risk alleles was 1.25 (95% confidence interval [CI], 1.21-1.29), with low to moderate heterogeneity. Age at disease diagnosis was a significant covariate, with ORs of 1.35 (95% CI, 1.30-1.40) for age 55 years or younger and 1.21 (95% CI, 1.16-1.25) for age 75 years or younger. For a 65-year-old man, the 10-year heart disease risk for 2 vs 1 at-risk alleles would be 13.2% vs 11%. For a 40-year-old woman, the 10-year heart disease risk for 2 vs 1 at-risk alleles would be 2.4% vs 2.0%. Nearly identical but inverse results were found when comparing 1 vs 0 at-risk alleles. Three studies showed net reclassification indexes ranging from -0.1% to 4.8%.
We found a statistically significant association between 9p21 SNPs and heart disease that varied by age at disease onset, but the magnitude of the association was small.
已有研究报道并重复验证了 9 号染色体 p21 单核苷酸多态性（SNP）与心脏病之间的关联。如果检测能够提高传统危险因素的风险评估效果，那么这可能为改善公众健康提供机会。
针对已发表文献进行目标性系统综述，评估其效应大小、异质性、发表偏倚和证据强度，并考虑检测是否具有临床应用价值。
通过 HuGE Navigator 电子检索，检索时限截至 2009 年 1 月，并查阅纳入文献的参考文献列表。
检测与冠心病/动脉粥样硬化或心肌梗死作为主要结局的 9p21SNP 的英文文献。纳入文献还提供了种族、参与者数量和计算比值比（OR）的数据。如果仅报告中间结局（如动脉粥样硬化）或所有参与者均存在疾病，则排除这些文献。最初确定了 25 篇文献，其中 16 篇被纳入。后续检索又确定了 6 篇文献。
由 2 位评审员独立进行数据提取，达成共识。使用已发表的威尼斯标准评估证据可信度。
对 22 篇文献中的 47 个独立数据集进行了分析，包括 35872 例病例和 95837 例对照。2 个风险等位基因个体的心脏病发病风险比（OR）汇总值为 1.25（95%置信区间[CI]，1.21-1.29），异质性低至中度。疾病诊断年龄是一个显著的协变量，55 岁及以下的 OR 为 1.35（95%CI，1.30-1.40），75 岁及以下的 OR 为 1.21（95%CI，1.16-1.25）。对于 65 岁的男性，2 个风险等位基因与 1 个风险等位基因相比，10 年心脏病发病风险为 13.2%比 11%。对于 40 岁的女性，2 个风险等位基因与 1 个风险等位基因相比，10 年心脏病发病风险为 2.4%比 2.0%。当比较 1 个风险等位基因与 0 个风险等位基因时，几乎得到了相同但相反的结果。3 项研究显示净重新分类指数范围为-0.1%至 4.8%。
我们发现 9p21SNP 与心脏病之间存在统计学显著关联，其与疾病发病年龄有关，但关联程度较小。
