Journal Article

Vitamin D Status, Filaggrin Genotype, and Cardiovascular Risk Factors: A Mendelian Randomization Approach

Menné, Torkil, Carlsen, Berit, Thyssen, Jacob P., Thuesen, Betina Heinsbæk, Melgaard, Michael, Johansen, Jeanne D., Husemoen, Lise Lotte Nystrup, Pisinger, Charlotta, Fenger, Mogens, Linneberg, Allan, Martinussen, Torben, Szecsi, Pal B., Fenger, Runa Vavia, Jørgensen, Torben, Skaaby, Tea, Stender, Steen

2013

Overview

Vitamin D deficiency is associated with increased cardiovascular disease risk in observational studies. Whether these associations are causal is not clear. Loss-of-function mutations in the filaggrin gene result in up to 10% higher serum vitamin D concentrations, supposedly due to a decreased UV-protection of the keratinocytes. We used a Mendelian randomization approach to estimate the causal effect of vitamin D status on serum lipids, blood pressure, body mass index, waist circumference, and the metabolic syndrome. Three population based studies were included, Monica10 (2,656 individuals aged 40-71 years), Inter99 (6,784 individuals aged 30-60 years), and Health2006 (3,471 individuals aged 18-69 years) conducted in 1993-94, 1999-2001, and 2006-2008, respectively. Participants were genotyped for the two most common filaggrin gene mutations in European descendants R501X and 2282del4, in all three studies and further for the R2447X mutation in the Inter99 and Health2006 studies. Filaggrin genotype was used as instrumental variable for vitamin D status. Baseline measurements of serum 25-hydroxyvitamin D were performed in all three studies. Instrumental variable analyses showed a 23.8% (95% confidence interval, CI 3.0, 48.6) higher HDL cholesterol level and a 30.5% (95% CI: 0.8, 51.3) lower serum level of triglycerides per doubling of vitamin D. These associations were, however, not statistically significant when applying the Bonferroni adjusted significance level. The remaining lipids showed non-significant changes in a favorable direction. Doubling of vitamin D gave a non-significantly lower odds ratio = 0.26 (95% CI: 0.06, 1.17) of the metabolic syndrome. There were no statistically significant causal effects of vitamin D status on blood pressure, body mass index, or waist circumference. Our results support a causal effect of higher vitamin D status on a more favorable lipid profile, although more studies in other populations are needed to confirm our results.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: 25-Hydroxyvitamin D / Adolescent / Adult / Aged / Biochemistry / Blood / Blood pressure / Body mass / Body mass index / Body size / Calciferol / Cardiovascular disease / Cardiovascular diseases / Cardiovascular Diseases - blood / Cardiovascular Diseases - genetics / Cholesterol / Confidence intervals / Diabetes / Disease prevention / Female / Filaggrin / Genetic Predisposition to Disease / Genotype / Genotype & phenotype / Health risks / High density lipoprotein / Hospitals / Humans / Intermediate Filament Proteins - genetics / Keratinocytes / Linear Models / Lipid metabolism / Lipids / Male / Medicine / Mendelian Randomization Analysis / Metabolic disorders / Metabolic syndrome / Middle Aged / Mutation / Observational studies / Population / Population studies / Randomization / Risk analysis / Risk Factors / Serum lipids / Statistical analysis / Statistical significance / Studies / Systematic review / Triglycerides / Vitamin D / Vitamin D - blood / Vitamin deficiency / Young Adult