Cluett Christie, McDermott Mary McGrae, Guralnik Jack, Ferrucci Luigi, Bandinelli Stefania, Miljkovic Iva, Zmuda Joseph M, Li Rongling, Tranah Greg, Harris Tamara, Rice Neil, Henley William, Frayling Timothy M, Murray Anna, Melzer David
Peninsula Medical School, Exeter, United Kingdom.
Circ Cardiovasc Genet. 2009 Aug;2(4):347-53. doi: 10.1161/CIRCGENETICS.108.825935. Epub 2009 Jun 23.
A common variant at chromosome 9p21 (tagged by the rs1333049 or rs10757278 single-nucleotide polymorphism) is strongly associated with myocardial infarction and major arterial aneurysms. An association with peripheral arterial disease (PAD) was also reported in a sample younger than 75 years, but this disappeared on removal of respondents with a myocardial infarction history, resulting in an odds ratio of 1.09 for PAD (P=0.075). We aimed at estimating the association of this variant with an Ankle-Brachial Index (ABI) and PAD in 3 older populations.
We used data from the InCHIANTI, Baltimore Longitudinal Study of Aging, and Health, Aging, and Body Composition studies. In 2630 white individuals (mean age, 76.4 years), the C allele at rs1333049 was associated with lower mean ABI measures and with an increased prevalence of PAD. These associations remained after removal of baseline and incident myocardial infarction cases over a 6-year follow-up for both ABI (-0.017 ABI units; 95% CI, -0.03 to -0.01; P = 1.3 x 10(-4)) and PAD (per allele odds ratio, 1.29; 95% CI, 1.06 to 1.56; P = 0.012). These associations also remained after adjustment for known atherosclerosis risk factors, including diabetes mellitus, smoking, hypercholesterolemia, and hypertension.
The C allele at rs1333049 is associated with an increased prevalence of PAD and lower mean ABI. This association was independent of the presence of diagnosed myocardial infarction and atherosclerotic risk factors in 3 older white populations.
9号染色体p21区域的一个常见变异（由rs1333049或rs10757278单核苷酸多态性标记）与心肌梗死和主要动脉动脉瘤密切相关。在一个年龄小于75岁的样本中也报道了该变异与外周动脉疾病（PAD）有关，但在排除有心肌梗死病史的受访者后这种关联消失了，导致PAD的优势比为1.09（P = 0.075）。我们旨在评估该变异在3个老年人群中与踝臂指数（ABI）及PAD的关联。
我们使用了来自基安蒂（InCHIANTI）研究、巴尔的摩老龄化纵向研究以及健康、老龄化和身体成分研究的数据。在2630名白人个体（平均年龄76.4岁）中，rs1333049位点的C等位基因与较低的平均ABI测量值以及PAD患病率增加相关。在对ABI（-0.017 ABI单位；95%可信区间，-0.03至-0.01；P = 1.3×10⁻⁴）和PAD（每个等位基因的优势比，1.29；95%可信区间，1.06至1.56；P = 0.012）进行为期6年的随访并排除基线和新发心肌梗死病例后，这些关联仍然存在。在对包括糖尿病、吸烟、高胆固醇血症和高血压等已知的动脉粥样硬化危险因素进行调整后，这些关联同样存在。
rs1333049位点的C等位基因与PAD患病率增加及较低的平均ABI相关。在3个老年白人人群中，这种关联独立于已诊断的心肌梗死和动脉粥样硬化危险因素的存在。
