Borné Yan, Muhammad Iram Faqir, Lorés-Motta Laura, Hedblad Bo, Nilsson Peter M, Melander Olle, de Jong Eiko K, Blom Anna M, den Hollander Anneke I, Engström Gunnar
Department of Clinical Sciences, Lund University, Sweden.
Department of Ophthalmology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, The Netherlands.
J Clin Endocrinol Metab. 2017 Dec 1;102(12):4477-4485. doi: 10.1210/jc.2017-00948.
This study explored whether complement factor 3 (C3) in plasma is associated with incidence of diabetes in a population-based cohort. We also identified genetic variants related to C3 and explored whether C3 and diabetes share common genetic determinants.
C3 was analyzed in plasma from 4368 nondiabetic subjects, 46 to 68 years old, from the Malmö Diet and Cancer Study. Incidence of diabetes was studied in relationship to C3 levels during 17.7± 4.4 years of follow-up. Genotypes associated with C3 were identified in a genome-wide association study. Diabetes Genetics Replication and Meta-Analysis and the European Genetic Database were used for in silico look-up.
In all, 538 (12.3%) subjects developed diabetes during 18 years of follow-up. High C3 was significantly associated with incidence of diabetes after risk factor adjustments (hazard ratio comparing 4th vs 1st quartile, 1.54 (95% confidence interval, 1.13 to 2.09; P = 0.005). C3 was associated with polymorphisms at the complement factor H locus (P < 10-8). However, no relationship with diabetes was observed for this locus. Another eight loci were associated with C3 with P < 10-5. One of them, the glucose kinase regulatory protein (GCKR) locus, has been previously associated with diabetes. The relationship between C3 levels and the GCKR locus was replicated in the European Genetic Database cohort.
Plasma concentration of C3 is a risk marker for incidence of diabetes. The results suggest that this association could, in part, be explained by pleiotropic effects related to the GCKR gene.
本研究探讨了基于人群的队列中血浆补体因子3（C3）是否与糖尿病发病率相关。我们还鉴定了与C3相关的基因变异，并探讨C3和糖尿病是否共享共同的遗传决定因素。
对来自马尔默饮食与癌症研究的4368名46至68岁非糖尿病受试者的血浆进行C3分析。在17.7±4.4年的随访期间，研究糖尿病发病率与C3水平的关系。在全基因组关联研究中鉴定与C3相关的基因型。使用糖尿病遗传学复制和荟萃分析以及欧洲遗传数据库进行电子查询。
在18年的随访中，共有538名（12.3%）受试者患糖尿病。在调整风险因素后，高C3与糖尿病发病率显著相关（比较第4四分位数与第1四分位数的风险比，1.54（95%置信区间，1.13至2.09；P = 0.005）。C3与补体因子H基因座的多态性相关（P < 10-8）。然而，未观察到该基因座与糖尿病的关系。另外8个基因座与C3相关，P < 10-5。其中之一，葡萄糖激酶调节蛋白（GCKR）基因座，此前已与糖尿病相关。C3水平与GCKR基因座之间的关系在欧洲遗传数据库队列中得到复制。
血浆C3浓度是糖尿病发病的风险标志物。结果表明，这种关联部分可能由与GCKR基因相关的多效性效应解释。
