Molecular Epidemiology and Science for Life Laboratory, Department of Medical Sciences, Uppsala University , Uppsala , Sweden.
Cardiovascular Epidemiology, Department of Medical Sciences, Uppsala University , Uppsala , Sweden.
Front Cardiovasc Med. 2015 Mar 5;2:11. doi: 10.3389/fcvm.2015.00011. eCollection 2015.
Several observational studies have shown an association between increased circulating homocysteine and risk of type 2 diabetes (T2D). We aimed to assess whether this relation is causal using genetic data from large populations of individuals of European descent.
We investigated the association between homocysteine concentrations and blood glucose, plasma insulin, T2D in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) cohort (n = 1,016). A score of five previously published single nucleotide polymorphisms (SNPs) from genes involved in homocysteine metabolism were utilized as genetic instrument for homocysteine concentrations. The effect estimate of this genetic score with T2D was determined using results from the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) consortium (including 34,840 cases and 114,981 controls). Further, the effects of the genetic score with fasting glucose and insulin were determined using results from the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) (up to 38,238 non-diabetic participants).
The genetic score provided a strong instrument for homocysteine concentrations (P = 2.7 × 10(-143), F = 650). In the PIVUS cohort, we found an association of homocysteine with fasting insulin [β = 0.056 (95% CI 0.021, 0.090), P = 0.001], but not with incident diabetes. We did not find any evidence of a causal effect of homocysteine on fasting glucose, fasting insulin, or T2D (P > 0.05 for all analyses) when using data from DIAGRAM or MAGIC studies.
No evidence of a causal relationship of levels of plasma homocysteine with fasting glucose, fasting insulin, or T2D was observed.
几项观察性研究表明，循环同型半胱氨酸水平升高与 2 型糖尿病（T2D）风险增加有关。我们旨在使用欧洲血统个体的大型人群遗传数据来评估这种关系是否具有因果关系。
我们在前瞻性血管研究乌普萨拉老年人队列（PIVUS）中调查了同型半胱氨酸浓度与血糖、血浆胰岛素、T2D 之间的关联（n=1016）。使用涉及同型半胱氨酸代谢的基因中之前发表的五个单核苷酸多态性（SNP）评分作为同型半胱氨酸浓度的遗传工具。使用糖尿病遗传学复制和荟萃分析（DIAGRAM）联盟（包括 34840 例病例和 114981 例对照）的结果来确定这种遗传评分与 T2D 的效应估计。此外，还使用代谢组学分析葡萄糖和胰岛素相关特征联盟（MAGIC）（多达 38238 名非糖尿病参与者）的结果来确定遗传评分与空腹血糖和胰岛素的作用。
遗传评分是同型半胱氨酸浓度的有力工具（P=2.7×10(-143)，F=650）。在 PIVUS 队列中，我们发现同型半胱氨酸与空腹胰岛素有关[β=0.056（95%CI 0.021，0.090），P=0.001]，但与新发糖尿病无关。当使用 DIAGRAM 或 MAGIC 研究的数据时，我们没有发现同型半胱氨酸对空腹血糖、空腹胰岛素或 T2D 有任何因果影响的证据（所有分析的 P>0.05）。
没有证据表明血浆同型半胱氨酸水平与空腹血糖、空腹胰岛素或 T2D 之间存在因果关系。
