Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts.
J Am Coll Cardiol. 2013 Feb 19;61(7):728-37. doi: 10.1016/j.jacc.2012.09.063. Epub 2013 Jan 9.
This study sought to investigate into the biologically plausible interaction between the common haptoglobin (Hp) polymorphism rs#72294371 and glycosylated hemoglobin (HbA(1c)) on risk of coronary heart disease (CHD).
Studies of the association between the Hp polymorphism and CHD report inconsistent results. Individuals with the Hp2-2 genotype produce Hp proteins with an impaired ability to prevent oxidative injury caused by elevated HbA(1c).
HbA(1c) concentration and Hp genotype were determined for 407 CHD cases matched 1:1 to controls (from the NHS [Nurses' Health Study]) and in a replication cohort of 2,070 individuals who served as the nontreatment group in the ICARE (Prevention of Cardiovascular Complications in Diabetic Patients With Vitamin E Treatment) study, with 29 CHD events during follow-up. Multivariate models were adjusted for lifestyle and CHD risk factors as appropriate. A pooled analysis was conducted of NHS, ICARE, and the 1 previously published analysis (a cardiovascular disease case-control sample from the Strong Heart Study).
In the NHS, Hp2-2 genotype (39% frequency) was strongly related to CHD risk only among individuals with elevated HbA(1c) (≥ 6.5%), an association that was similar in the ICARE trial and the Strong Heart Study. In a pooled analysis, participants with both the Hp2-2 genotype and elevated HbA(1c) had a relative risk of 7.90 (95% confidence interval: 4.43 to 14.10) for CHD compared with participants with both an Hp1 allele and HbA(1c) <6.5% (p for interaction = 0.004), whereas the Hp2-2 genotype with HbA(1c) <6.5% was not associated with risk (relative risk: 1.34 [95% confidence interval: 0.73 to 2.46]).
Hp genotype was a significant predictor of CHD among individuals with elevated HbA(1c).
本研究旨在探讨常见的触珠蛋白（Hp）多态性 rs#72294371 与糖化血红蛋白（HbA(1c)）之间可能存在的生物学相互作用，以探究其对冠心病（CHD）的风险。
有关 Hp 多态性与 CHD 相关性的研究结果并不一致。Hp2-2 基因型个体产生的 Hp 蛋白，其防止由 HbA(1c)升高引起的氧化损伤的能力受损。
对 407 例 CHD 病例（来自 NHS[护士健康研究]）和作为 ICARE（维生素 E 治疗糖尿病患者心血管并发症预防）研究非治疗组的 2070 例个体（29 例 CHD 事件随访）进行了 HbA(1c)浓度和 Hp 基因型测定。适当调整多变量模型以适应生活方式和 CHD 风险因素。对 NHS、ICARE 和之前发表的一项分析（来自 Strong Heart 研究的心血管疾病病例对照样本）进行了汇总分析。
在 NHS 中，Hp2-2 基因型（频率 39%）仅与 HbA(1c)升高（≥6.5%）的个体的 CHD 风险密切相关，而 ICARE 试验和 Strong Heart 研究中也存在相似的关联。在汇总分析中，与同时具有 Hp1 等位基因和 HbA(1c)<6.5%的参与者相比，同时具有 Hp2-2 基因型和 HbA(1c)升高的参与者发生 CHD 的相对风险为 7.90（95%置信区间：4.43 至 14.10）（p 交互作用=0.004），而 Hp2-2 基因型且 HbA(1c)<6.5%与风险无关（相对风险：1.34[95%置信区间：0.73 至 2.46]）。
在 HbA(1c)升高的个体中，Hp 基因型是 CHD 的一个重要预测因子。
