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

Liefaard MC, Ligthart S, Vitezova A, Hofman A, Uitterlinden AG, Kiefte-de Jong JC, Franco OH, Zillikens MC, Dehghan A - PLoS ONE (2015)

Bottom Line: Vitamin D deficiency is widely prevalent and has been associated with many diseases.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands; Netherlands Institute for Health Sciences, 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.

No MeSH data available.


Related in: MedlinePlus

Concept of Mendelian randomization.
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pone.0131740.g001: Concept of Mendelian randomization.

Mentions: Conclusions about causality cannot be drawn merely based on the presence of an association in an observational design. A complementary alternative is to apply the Mendelian randomization approach, in which the relationship between a genetic determinant of a predictor variable and a specific outcome is studied (Fig 1).[16, 17] If there is indeed a causal effect of vitamin D on inflammation as measured with C-reactive protein (CRP), genetic determinants related to vitamin D should be associated with CRP levels In turn, if inflammation would lower vitamin D levels, genetic determinants of CRP would be expected to be associated with vitamin D levels. These associations are less prone to confounding, since the genetic variants are inherited randomly and do not associate with any other factors. Moreover, reverse causation is unlikely, due to the constant nature of genetic variants over their life course.[16, 17]


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

Liefaard MC, Ligthart S, Vitezova A, Hofman A, Uitterlinden AG, Kiefte-de Jong JC, Franco OH, Zillikens MC, Dehghan A - PLoS ONE (2015)

Concept of Mendelian randomization.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492676&req=5

pone.0131740.g001: Concept of Mendelian randomization.
Mentions: Conclusions about causality cannot be drawn merely based on the presence of an association in an observational design. A complementary alternative is to apply the Mendelian randomization approach, in which the relationship between a genetic determinant of a predictor variable and a specific outcome is studied (Fig 1).[16, 17] If there is indeed a causal effect of vitamin D on inflammation as measured with C-reactive protein (CRP), genetic determinants related to vitamin D should be associated with CRP levels In turn, if inflammation would lower vitamin D levels, genetic determinants of CRP would be expected to be associated with vitamin D levels. These associations are less prone to confounding, since the genetic variants are inherited randomly and do not associate with any other factors. Moreover, reverse causation is unlikely, due to the constant nature of genetic variants over their life course.[16, 17]

Bottom Line: Vitamin D deficiency is widely prevalent and has been associated with many diseases.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands; Netherlands Institute for Health Sciences, 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.

No MeSH data available.


Related in: MedlinePlus