孟德尔随机化分析评估结合珠蛋白对中国 2 型糖尿病患者大血管病变的因果效应。
Mendelian randomization analysis to assess a causal effect of haptoglobin on macroangiopathy in Chinese type 2 diabetes patients.
机构信息
Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, People's Republic of China.
Institute for Metabolic Disease, Fengxian Central Hospital Affiliated to Southern Medical University, 6600 Nanfeng Road, Shanghai, 201499, People's Republic of China.
出版信息
Cardiovasc Diabetol. 2018 Jan 16;17(1):14. doi: 10.1186/s12933-018-0662-7.
BACKGROUND
Haptoglobin (Hp) functions as an antioxidant by binding with haemoglobin. We investigated whether serum Hp has a causal effect on macroangiopathy via Mendelian randomization (MR) analysis with common variants of the Hp gene in Chinese patients with type 2 diabetes.
METHODS
A total of 5687 type 2 diabetes patients were recruited and genotyped for the Hp gene. Clinical features and vascular imaging tests were applied to diagnose macroangiopathy. The association between common Hp genotypes and macroangiopathy was analyzed in the whole population. Serum Hp levels were measured by enzyme-linked immunosorbent assay in a subset of 935 patients. We individually analyzed the correlations among Hp levels, Hp genotypes and macroangiopathy. Further, 8-hydroxy-2'-deoxyguanosine (8-OHdG), an oxidative marker of DNA damage, was examined to evaluate the levels of oxidative stress.
RESULTS
Common Hp genotypes were correlated with macroangiopathy (OR = 1.140 [95% CI 1.005-1.293], P = 0.0410 for the Hp 1 allele). Serum Hp levels were associated with both common Hp genotypes (P = 3.55 × 10) and macroangiopathy (OR = 2.123 [95% CI 1.098-4.102], P = 0.0252) in the subset of 935 patients. In the MR analysis, the directional trends of the observed and predicted relationships between common Hp genotypes and macroangiopathy were the same (OR 1.357 and 1.130, respectively). Furthermore, common Hp genotypes and Hp levels were associated with serum 8-OHdG levels (P = 0.0001 and 0.0084, respectively).
CONCLUSIONS
Our study provides evidence for a causal relationship between serum Hp levels and macroangiopathy in Chinese type 2 diabetes patients by MR analysis.
背景
触珠蛋白 (Hp) 通过与血红蛋白结合发挥抗氧化作用。我们通过对中国 2 型糖尿病患者的 Hp 基因常见变异进行孟德尔随机分析，研究血清 Hp 是否通过因果关系对大血管疾病产生影响。
方法
共招募了 5687 名 2 型糖尿病患者，并对 Hp 基因进行了基因分型。临床特征和血管成像检查用于诊断大血管疾病。在全人群中分析常见 Hp 基因型与大血管疾病的关系。在 935 名患者的亚组中，通过酶联免疫吸附试验测量血清 Hp 水平。我们分别分析了 Hp 水平、Hp 基因型与大血管疾病之间的相关性。此外，还检测了氧化应激的 DNA 损伤标志物 8-羟基-2'-脱氧鸟苷 (8-OHdG) 的水平。
结果
常见的 Hp 基因型与大血管疾病相关（OR=1.140[95%CI1.005-1.293]，P=0.0410 对于 Hp1 等位基因）。在 935 名患者的亚组中，血清 Hp 水平与常见 Hp 基因型（P=3.55×10）和大血管疾病（OR=2.123[95%CI1.098-4.102]，P=0.0252）相关。在 MR 分析中，观察到的和预测的常见 Hp 基因型与大血管疾病之间的关系的方向趋势是一致的（OR1.357 和 1.130）。此外，常见的 Hp 基因型和 Hp 水平与血清 8-OHdG 水平相关（P=0.0001 和 0.0084）。
结论
通过 MR 分析，我们的研究为中国 2 型糖尿病患者血清 Hp 水平与大血管疾病之间的因果关系提供了证据。
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