Vitamin D and C-Reactive Protein: A Mendelian Randomization Study

Marte C Liefaard; Symen Ligthart; Anna Vitezova; Albert Hofman; André G Uitterlinden; Jessica C Kiefte-de Jong; Oscar H Franco; M Carola Zillikens; Abbas Dehghan

doi:10.1371/journal.pone.0131740

Vitamin D and C-Reactive Protein: A Mendelian Randomization Study

PLoS One. 2015 Jul 6;10(7):e0131740. doi: 10.1371/journal.pone.0131740. eCollection 2015.

Authors

Marte C Liefaard¹, Symen Ligthart², Anna Vitezova², Albert Hofman², André G Uitterlinden³, Jessica C Kiefte-de Jong², Oscar H Franco², M Carola Zillikens⁴, Abbas Dehghan²

Affiliations

¹ Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands; Netherlands Institute for Health Sciences, Rotterdam, the Netherlands.
² Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
³ Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands; Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands.
⁴ Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands.

Abstract

Vitamin D deficiency is widely prevalent and has been associated with many diseases. It has been suggested that vitamin D has effects on the immune system and inhibits inflammation. The aim of our study was to investigate whether vitamin D has an inhibitory effect on systemic inflammation by assessing the association between serum levels of vitamin D and C-reactive protein. We studied the association between serum 25-hydroxyvitamin D and C-reactive protein through linear regression in 9,649 participants of the Rotterdam Study, an observational, prospective population-based cohort study. We used genetic variants related to vitamin D and CRP to compute a genetic risk score and perform bi-directional Mendelian randomization analysis. In linear regression adjusted for age, sex, cohort and other confounders, natural log-transformed CRP decreased with 0.06 (95% CI: -0.08, -0.03) unit per standard deviation increase in 25-hydroxyvitamin D. Bi-directional Mendelian randomization analyses showed no association between the vitamin D genetic risk score and lnCRP (Beta per SD = -0.018; p = 0.082) or the CRP genetic risk score and 25-hydroxyvitamin D (Beta per SD = 0.001; p = 0.998). In conclusion, higher levels of Vitamin D are associated with lower levels of C-reactive protein. In this study we did not find evidence for this to be the result of a causal relationship.

Publication types

Observational Study
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aged, 80 and over
C-Reactive Protein / metabolism*
Cohort Studies
Female
Genotype
Humans
Linear Models
Male
Mendelian Randomization Analysis
Middle Aged
Vitamin D / blood*
Vitamin D Deficiency / blood*
Vitamin D Deficiency / genetics

Substances

Vitamin D
C-Reactive Protein

Grants and funding

The Rotterdam Study is supported by the Erasmus Medical Center and Erasmus University Rotterdam; the Netherlands Organization for Scientific Research (NWO); the Netherlands Organization for Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly (RIDE); the Netherlands Heart Foundation; the Ministry of Education, Culture and Science; the Ministry of Health Welfare and Sports; the European Commission; and the Municipality of Rotterdam. DSM Nutritional Products AG, Kaiseraugst, Switzerland, sponsored the Vitamin D serum analyses. Abbas Dehghan is supported by NWO grant (veni, 916.12.154) and the EUR Fellowship. O.H. Franco works in ErasmusAGE, a center for aging research across the life course funded by Nestlé Nutrition (Nestec Ltd.); Metagenics Inc.; and AXA. Nestlé Nutrition (Nestec Ltd.); Metagenics Inc.; and AXA had no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review or approval of the manuscript. DSM Nutritional Products AG had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.