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Olle Melander

Principal investigator

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Complement C3 Associates With Incidence of Diabetes, but No Evidence of a Causal Relationship

Author

  • Yan Borné
  • Iram Faqir Muhammad
  • Laura Lorés-Motta
  • Bo Hedblad
  • Peter M. Nilsson
  • Olle Melander
  • Eiko K. de Jong
  • Anna M. Blom
  • Anneke I. den Hollander
  • Gunnar Engström

Summary, in English

Purpose: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Department/s

  • Cardiovascular Research - Epidemiology
  • Internal Medicine - Epidemiology
  • Cardiovascular Research - Hypertension
  • Protein Chemistry, Malmö
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • EpiHealth: Epidemiology for Health

Publishing year

2017-12-01

Language

English

Pages

4477-4485

Publication/Series

The Journal of clinical endocrinology and metabolism

Volume

102

Issue

12

Document type

Journal article

Publisher

Oxford University Press

Topic

  • Endocrinology and Diabetes

Status

Published

Research group

  • Cardiovascular Research - Epidemiology
  • Internal Medicine - Epidemiology
  • Cardiovascular Research - Hypertension
  • Protein Chemistry, Malmö

ISBN/ISSN/Other

  • ISSN: 1945-7197