Unit of Endocrinology, IRCCS Casa Sollievo della Sofferenza San Giovanni Rotondo, Italy.
Diabetes. 2011 Mar;60(3):1000-7. doi: 10.2337/db10-1300. Epub 2011 Jan 31.
Insulin resistance (IR) and cardiovascular disease may share a common genetic background. We investigated the role of IR-associated ENPP1 K121Q polymorphism (rs1044498) on cardiovascular disease in high-risk individuals.
A prospective study (average follow-up, 37 months) was conducted for major cardiovascular events (myocardial infarction [MI], stroke, cardiovascular death) from the Gargano Heart Study (GHS; n = 330 with type 2 diabetes and coronary artery disease), the Tor Vergata Atherosclerosis Study (TVAS; n = 141 who had MI), and the Cardiovascular Risk Extended Evaluation in Dialysis (CREED) database (n = 266 with end-stage renal disease). Age at MI was investigated in cross-sectional studies of 339 type 2 diabetic patients (n = 169 from Italy, n = 170 from the U.S.).
Incidence of cardiovascular events per 100 person--years was 4.2 in GHS, 10.8 in TVAS, and 11.7 in CREED. Hazard ratios (HRs) for KQ+QQ versus individuals carrying the K121/K121 genotype (KK) individuals were 1.47 (95% CI 0.80-2.70) in GHS, 2.31 (95% CI 1.22-4.34) in TVAS, and 1.36 (95% CI 0.88-2.10) in CREED, and 1.56 (95% CI 1.15-2.12) in the three cohorts combined. In the 395 diabetic patients, the Q121 variant predicted cardiovascular events among obese but not among nonobese individuals (HR 5.94 vs. 0.62, P = 0.003 for interaction). A similar synergism was observed in cross-sectional studies, with age at MI being 3 years younger in Q121 carriers than in KK homozygotes among obese but not among nonobese patients (P = 0.035 for interaction).
The ENPP1 K121Q polymorphism is an independent predictor of major cardiovascular events in high-risk individuals. In type 2 diabetes, this effect is exacerbated by obesity. Future larger studies are needed to confirm our finding.
胰岛素抵抗（IR）和心血管疾病可能具有共同的遗传背景。我们研究了与 IR 相关的 ENPP1 K121Q 多态性（rs1044498）对高危个体心血管疾病的作用。
对 Gargano 心脏研究（GHS；n=330 例 2 型糖尿病合并冠状动脉疾病）、Tor Vergata 动脉粥样硬化研究（TVAS；n=141 例心肌梗死）和心血管风险扩展评估在透析中的研究（CREED）数据库（n=266 例终末期肾病）进行了主要心血管事件（心肌梗死[MI]、中风、心血管死亡）的前瞻性研究（平均随访时间 37 个月）。在来自意大利的 169 例和来自美国的 170 例 2 型糖尿病患者的横断面研究中，调查了 MI 的发病年龄。
GHS 中每 100 人-年的心血管事件发生率为 4.2，TVAS 中为 10.8，CREED 中为 11.7。KQ+QQ 与携带 K121/K121 基因型（KK）个体相比的危险比（HR）分别为 GHS 中 1.47（95%CI 0.80-2.70），TVAS 中 2.31（95%CI 1.22-4.34），CREED 中 1.36（95%CI 0.88-2.10），以及三个队列的合并结果 1.56（95%CI 1.15-2.12）。在 395 例糖尿病患者中，Q121 变体预测肥胖者而非非肥胖者的心血管事件（HR 5.94 与 0.62，P=0.003 交互作用）。在横断面研究中也观察到类似的协同作用，肥胖患者中 Q121 携带者的 MI 发病年龄比 KK 纯合子年轻 3 岁，但在非肥胖患者中则不然（交互作用 P=0.035）。
ENPP1 K121Q 多态性是高危个体主要心血管事件的独立预测因子。在 2 型糖尿病中，这种影响在肥胖者中更为严重。需要进行更大的研究来证实我们的发现。
