Background: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.Methods: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).Results: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).Conclusions: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.

中文翻译：

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在非随机前瞻性对照瑞典肥胖受试者研究中，9p21.3 冠状动脉疾病位点确定了从减肥手术中获益的患者。

背景：染色体 9p21.3 的序列变异在几个人群中占心肌梗死 (MI) 的 20%。尽管 9p21.3 基因座赋予的风险似乎独立于传统风险因素起作用，但研究表明 9p21.3 与 MI 之间的关联会受到葡萄糖稳态和生活方式的影响。我们检查了 9p21.3 变体 rs1333049 以及先前确定的预测因子空腹胰岛素是否会改变减肥手术对 MI 发病率的预防作用。 SOS 研究（瑞典肥胖受试者）。MI 发病率是使用国家登记册确定的。中位随访时间为 21 年（四分位距为 18-24 年）。结果：总体而言，随访期间发生了 366 次 MI。P = 0.008）。相比之下，非携带者 (GG) 在治疗组之间的 MI 发生率上没有显着差异（风险比 = 1.28 [0.86–1.90]，P = 0.227；治疗与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 [17 mmol/L]）的携带者的 MI 发生率显着高于空腹胰岛素较低的携带者（风险比 = 0.58 [0.42–0.78]，P <0.001，交互作用P=0.031。结论：在 SOS 队列中，具有染色体 9p21.3 rs1333049 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.clinicaltrials .gov。唯一标识符：NCT01479452。