Paynter Nina P, Chasman Daniel I, Buring Julie E, Shiffman Dov, Cook Nancy R, Ridker Paul M
Brigham and Women's Hospital, 900 Commonwealth Avenue East, Boston, MA 02215, USA.
Ann Intern Med. 2009 Jan 20;150(2):65-72. doi: 10.7326/0003-4819-150-2-200901200-00003.
Although genetic variation at chromosome 9p21.3 is associated with incident cardiovascular disease, it is unclear whether screening for this polymorphism improves risk prediction.
To determine whether knowledge of variation at chromosome 9p21.3 provides predictive information beyond that from other readily available risk factors.
Prospective cohort study.
United States.
22 129 female white health professionals participating in the Women's Genome Health Study, initially without any major chronic disease, who were prospectively followed over a median of 10.2 years for incident cardiovascular disease.
Polymorphism at rs10757274 in chromosome 9p21.3 and additional cardiovascular disease risk factors (blood pressure, smoking status, diabetes, blood levels of cholesterol, high-sensitivity C-reactive protein, and family history of premature myocardial infarction).
Polymorphism at rs10757274 was associated with an adjusted hazard ratio for incident cardiovascular disease of 1.25 (95% CI, 1.04 to 1.51) for the AG genotype and 1.32 (CI, 1.07 to 1.63) for the GG genotype. However, the addition of the genotype to a prediction model based on traditional risk factors, high-sensitivity C-reactive protein, and family history of premature myocardial infarction had no effect on model discrimination as measured by the c-index (0.807 to 0.809) and did not improve the Net Reclassification Improvement score (-0.2%; P = 0.59) or the Integrated Discrimination Improvement score (0.0; P = 0.18).
Study participants were all white women.
In this large prospective cohort of white women, genetic variation in chromosome 9p21.3 was associated with incident cardiovascular disease but did not improve on the discrimination or classification of predicted risk achieved with traditional risk factors, high-sensitivity C-reactive protein, and family history of premature myocardial infarction.
尽管9号染色体p21.3区域的基因变异与心血管疾病的发生有关，但尚不清楚筛查这种多态性是否能改善风险预测。
确定9号染色体p21.3区域变异的相关信息是否能提供超出其他常用风险因素的预测信息。
前瞻性队列研究。
美国。
22129名参与女性基因组健康研究的白人女性健康专业人员，最初无任何重大慢性病，对其进行前瞻性随访，中位随访时间为10.2年，观察心血管疾病的发生情况。
9号染色体p21.3区域rs10757274位点的多态性以及其他心血管疾病风险因素（血压、吸烟状况、糖尿病、胆固醇水平、高敏C反应蛋白以及早发心肌梗死家族史）。
rs10757274位点的多态性与心血管疾病发生的校正风险比，AG基因型为1.25（95%可信区间为1.04至1.51），GG基因型为1.32（可信区间为1.07至1.63）。然而，将该基因型添加到基于传统风险因素、高敏C反应蛋白和早发心肌梗死家族史的预测模型中，用c指数衡量时对模型辨别能力无影响（0.807至0.809），且未改善净重新分类改善评分（-0.2%；P = 0.59）或综合辨别改善评分（0.0；P = 0.18）。
研究参与者均为白人女性。
在这个大型白人女性前瞻性队列中，9号染色体p21.3区域的基因变异与心血管疾病的发生有关，但在辨别能力或预测风险分类方面，并未优于传统风险因素、高敏C反应蛋白和早发心肌梗死家族史所达到的效果。
