Molecular Genetics and Genomics Program, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157, USA.
Cardiovasc Diabetol. 2013 Feb 11;12:31. doi: 10.1186/1475-2840-12-31.
Haptoglobin (HP) is an acute phase protein that binds to freely circulating hemoglobin. HP exists as two distinct forms, HP1 and HP2. The longer HP2 form has been associated with cardiovascular (CVD) events and mortality in individuals with type 2 diabetes (T2DM).
This study examined the association of HP genotypes with subclinical CVD, T2DM risk, and associated risk factors in a T2DM-enriched sample. Haptoglobin genotypes were determined in 1208 European Americans (EA) from 473 Diabetes Heart Study (DHS) families via PCR. Three promoter SNPs (rs5467, rs5470, and rs5471) were also genotyped.
Analyses revealed association between HP2-2 duplication and increased carotid intima-media thickness (IMT; p = 0.001). No association between HP and measures of calcified arterial plaque were observed, but the HP polymorphism was associated with triglyceride concentrations (p = 0.005) and CVD mortality (p = 0.04). We found that the HP2-2 genotype was associated with increased T2DM risk with an odds ratio (OR) of 1.49 (95% CI 1.18-1.86, p = 6.59x10(-4)). Promoter SNPs were not associated with any traits.
This study suggests association between the HP duplication and IMT, triglycerides, CVD mortality, and T2DM in an EA population enriched for T2DM. Lack of association with atherosclerotic calcified plaque likely reflect differences in the pathogenesis of these CVD phenotypes. HP variation may contribute to the heritable risk for CVD complications in T2DM.
触珠蛋白（HP）是一种结合游离循环血红蛋白的急性期蛋白。HP 有两种不同的形式，HP1 和 HP2。较长的 HP2 形式与 2 型糖尿病（T2DM）个体的心血管（CVD）事件和死亡率有关。
本研究在 T2DM 丰富的样本中，检查了 HP 基因型与亚临床 CVD、T2DM 风险及其相关危险因素的关系。通过 PCR 确定了来自 473 项糖尿病心脏研究（DHS）家族的 1208 名欧洲裔美国人（EA）的触珠蛋白基因型。还对 3 个启动子 SNP（rs5467、rs5470 和 rs5471）进行了基因分型。
分析显示 HP2-2 重复与颈动脉内膜中层厚度（IMT）增加之间存在关联（p = 0.001）。没有发现 HP 与钙化动脉斑块测量值之间的相关性，但 HP 多态性与甘油三酯浓度（p = 0.005）和 CVD 死亡率（p = 0.04）相关。我们发现，HP2-2 基因型与 T2DM 风险增加相关，优势比（OR）为 1.49（95%置信区间 1.18-1.86，p = 6.59x10(-4))。启动子 SNP 与任何特征均无关。
本研究表明，在富含 T2DM 的 EA 人群中，HP 重复与 IMT、甘油三酯、CVD 死亡率和 T2DM 之间存在相关性。与动脉粥样硬化钙化斑块缺乏相关性可能反映了这些 CVD 表型发病机制的差异。HP 变异可能导致 T2DM 患者 CVD 并发症的遗传风险增加。
