Exposing the Causal Effect of C-Reactive Protein on the Risk of Type 2 Diabetes Mellitus: A Mendelian Randomization Study
Exposing the Causal Effect of C-Reactive Protein on the Risk of Type 2 Diabetes Mellitus: A Mendelian Randomization Study
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DOI：
10.3389/fgene.2018.00657
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发表时间：
2018-12-20
影响因子：
3.7
通讯作者：
Zhang, Jun
中科院分区：
文献类型：
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作者：
Cheng, Liang;Zhuang, He;Zhang, Jun
作为炎症的生物标志物，C反应蛋白（CRP）因其在2型糖尿病（T2DM）发病中的作用而备受关注。前瞻性研究观察到血清CRP水平与T2DM发病率呈正相关。最近有研究报道，治疗T2DM的药物也可以降低血清CRP水平。然而，目前尚不清楚高 CRP 水平是否会导致 T2DM。为了评估这一点，我们使用遗传变异作为工具变量（IV）进行了孟德尔随机化（MR）分析。从全基因组研究和复制研究中获得了显着相关的 CRP 单核苷酸多态性 (SNP)。其中，17,967 名参与者被用于全基因组关联研究 (GWAS)，另外 14,747 名参与者被用于复制识别与 CRP 水平相关的 SNP。 SNP 与 T2DM 之间的关联来自糖尿病遗传学复制和荟萃分析 (DIAGRAM) 联盟。去除连锁不平衡（LD）和T2DM相关SNP中的SNP后，剩余的4个CRP相关SNP被视为IV。为了评估这些 IV 对通过 CRP 发生 T2DM 风险的综合影响，采用了惩罚稳健逆方差加权 (IVW) 方法。综合结果（OR 1.114048；95% CI 1.058656 至 1.172338；P = 0.024）表明，高水平的 CRP 显着增加 T2DM 的风险。在随后对CRP与1型糖尿病（T1DM）关系的分析中，汇总结果（OR 1.017145；95% CI 0.9066489至1.14225；P = 0.909）支持CRP水平不能决定发生T1DM的风险。
As a biomarker of inflammation, C-reactive protein (CRP) has attracted much attention due to its role in the incidence of type 2 diabetes mellitus (T2DM). Prospective studies have observed a positive correlation between the level of serum CRP and the incidence of T2DM. Recently, studies have reported that drugs for curing T2DM can also decrease the level of serum CRP. However, it is not yet clear whether high CRP levels cause T2DM. To evaluate this, we conducted a Mendelian randomization (MR) analysis using genetic variations as instrumental variables (IVs). Significantly associated single nucleotide polymorphisms (SNPs) of CRP were obtained from a genome-wide study and a replication study. Therein, 17,967 participants were utilized for the genome-wide association study (GWAS), and another 14,747 participants were utilized for the replication of identifying SNPs associated with CRP levels. The associations between SNPs and T2DM were from the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) consortium. After removing SNPs in linkage disequilibrium (LD) and T2DM-related SNPs, the four remaining CRP-related SNPs were deemed as IVs. To evaluate the pooled influence of these IVs on the risk of developing T2DM through CRP, the penalized robust inverse-variance weighted (IVW) method was carried out. The combined result (OR 1.114048; 95% CI 1.058656 to 1.172338; P = 0.024) showed that high levels of CRP significantly increase the risk of T2DM. In the subsequent analysis of the relationship between CRP and type 1 diabetes mellitus (T1DM), the pooled result (OR 1.017145; 95% CI 0.9066489 to 1.14225; P = 0.909) supported that CRP levels cannot determine the risk of developing T1DM.