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Abstract：
Sequence variation at chromosome 9p21.3 accounts for 20% of myocardial infarctions (MIs) in several populations. Whereas the risk conferred by the 9p21.3 locus appears to act independently of traditional risk factors, studies suggest that the association between 9p21.3 and MI is modified by glucose homeostasis and lifestyle. We examined if the 9p21.3 variant rs1333049, along with the previously identified predictor fasting insulin, modifies the preventive effect of bariatric surgery on MI incidence.
rs1333049 was genotyped in 1852 patients treated by bariatric surgery and 1803 controls given usual care in the SOS study (Swedish Obese Subjects). MI incidence was determined using national registers. Median follow-up was 21 years (interquartile range 18-24 years).
Overall, 366 MIs occurred during follow-up. Among rs1333049 risk-allele carriers (CC+GC), the incidence of MI was reduced in the surgery group compared with the control group (hazard ratio=0.72 [95% CI, 0.57-0.92], P=0.008). By contrast, noncarriers (GG) showed no significant differences in MI incidence between the treatment groups (hazard ratio=1.28 [0.86-1.90], P=0.227; interaction between treatment and the risk-allele P=0.016). In addition, carriers with higher fasting insulin (above the median [17 mmol/L]) experienced significantly higher MI incidence than carriers with lower fasting insulin (hazard ratio=0.58 [0.42-0.78], P<0.001, interaction P=0.031).
In the SOS cohort, patients with the chromosome 9p21.3 rs1333049 risk allele together with high fasting insulin levels benefitted from bariatric surgery in terms of reduced incidence of MI. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01479452.
rs1333049 was genotyped in 1852 patients treated by bariatric surgery and 1803 controls given usual care in the SOS study (Swedish Obese Subjects). MI incidence was determined using national registers. Median follow-up was 21 years (interquartile range 18-24 years).
Overall, 366 MIs occurred during follow-up. Among rs1333049 risk-allele carriers (CC+GC), the incidence of MI was reduced in the surgery group compared with the control group (hazard ratio=0.72 [95% CI, 0.57-0.92], P=0.008). By contrast, noncarriers (GG) showed no significant differences in MI incidence between the treatment groups (hazard ratio=1.28 [0.86-1.90], P=0.227; interaction between treatment and the risk-allele P=0.016). In addition, carriers with higher fasting insulin (above the median [17 mmol/L]) experienced significantly higher MI incidence than carriers with lower fasting insulin (hazard ratio=0.58 [0.42-0.78], P<0.001, interaction P=0.031).
In the SOS cohort, patients with the chromosome 9p21.3 rs1333049 risk allele together with high fasting insulin levels benefitted from bariatric surgery in terms of reduced incidence of MI. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01479452.
摘要：
9p21.3染色体上的序列变异占几个人群中心肌梗塞（MIs）的20％。而9p21.3位点赋予的风险似乎独立于传统风险因素，研究表明,9p21.3和MI之间的关联可通过葡萄糖稳态和生活方式改变.我们检查了9p21.3变体rs1333049，以及先前确定的预测空腹胰岛素，改变减肥手术对MI发生率的预防作用。
在SOS研究（瑞典肥胖受试者）中，对1852例接受减肥手术治疗的患者和1803例接受常规护理的对照进行了rs1333049的基因分型。MI发病率使用国家登记册确定。中位随访时间为21年（四分位距18-24年）。
总的来说，随访期间发生366次MI。在rs1333049风险等位基因携带者(CC+GC)中，与对照组相比，手术组的MI发生率降低(风险比=0.72[95%CI,0.57-0.92],P=0.008)。相比之下,非携带者（GG）在治疗组之间的MI发生率没有显着差异（风险比=1.28[0.86-1.90]，P=0.227；治疗和风险等位基因之间的相互作用P=0.016）。此外,空腹胰岛素较高（高于中位数[17mmol/L]）的携带者的MI发生率明显高于空腹胰岛素较低的携带者（危险比=0.58[0.42-0.78]，P<0.001,交互作用P=0.031)。
在SOS队列中，具有9p21.3rs1333049染色体风险等位基因和高空腹胰岛素水平的患者在降低MI发生率方面受益于减肥手术.注册：URL：https://www。临床试验.gov.唯一标识符：NCT01479452。
在SOS研究（瑞典肥胖受试者）中，对1852例接受减肥手术治疗的患者和1803例接受常规护理的对照进行了rs1333049的基因分型。MI发病率使用国家登记册确定。中位随访时间为21年（四分位距18-24年）。
总的来说，随访期间发生366次MI。在rs1333049风险等位基因携带者(CC+GC)中，与对照组相比，手术组的MI发生率降低(风险比=0.72[95%CI,0.57-0.92],P=0.008)。相比之下,非携带者（GG）在治疗组之间的MI发生率没有显着差异（风险比=1.28[0.86-1.90]，P=0.227；治疗和风险等位基因之间的相互作用P=0.016）。此外,空腹胰岛素较高（高于中位数[17mmol/L]）的携带者的MI发生率明显高于空腹胰岛素较低的携带者（危险比=0.58[0.42-0.78]，P<0.001,交互作用P=0.031)。
在SOS队列中，具有9p21.3rs1333049染色体风险等位基因和高空腹胰岛素水平的患者在降低MI发生率方面受益于减肥手术.注册：URL：https://www。临床试验.gov.唯一标识符：NCT01479452。
