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Elevated remnant cholesterol in 25-hydroxyvitamin D deficiency in the general population: Mendelian randomization

Esther M Ooi¹, Shoaib Afzal¹, Børge G Nordestgaard²

¹From the Department of Clinical Biochemistry (E.M.O., S.A., B.G.N.), The Copenhagen General Population Study (E.M.O., S.A., B.G.N.), Herlev Hospital, Herlev, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark (S.A., B.G.N.); The Copenhagen City Heart Study, Frederiksberg Hospital, Frederiksberg, Denmark (B.G.N.); and School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia (E.M.O.).

Circulation. Cardiovascular Genetics

|July 29, 2014

Abstract

Background:

Low plasma 25-hydroxyvitamin D [25(OH)D] levels are associated with high cardiovascular risk. This may be because that low 25(OH)D levels are associated with high levels of atherogenic lipoproteins, but whether these 2 risk factors are genetically associated is unknown. We tested this hypothesis.

Methods And Results:

Using a Mendelian randomization approach, potential genetic associations between plasma levels of atherogenic lipoproteins and 25(OH)D were examined in ≤85,868 white, Danish individuals in whom we genotyped for variants affecting plasma levels of 25(OH)D, nonfasting remnant cholesterol, low-density lipoprotein-cholesterol, and high-density lipoprotein-cholesterol. Lipoprotein levels were measured in all and 25(OH)D levels in 31,435. A doubling in nonfasting remnant cholesterol levels was observationally and genetically associated with -6.0%(95% confidence interval [CI], -6.5% to -5.5%) and -8.9% (95% CI, -15% to -2.3%) lower plasma 25(OH)D levels. For low-density lipoprotein-cholesterol levels, corresponding values were -4.6% (95% CI, -5.4% to -3.7%) observationally and -11% (95% CI, -29% to +6.9%) genetically. In contrast, a halving in high-density lipoprotein-cholesterol levels was observationally associated with -1.5% (95% CI, -2.2% to -0.7%) lower but genetically associated with +20% (95% CI, +7.4% to +34%) higher plasma 25(OH)D levels. Plasma levels of lipoprotein(a) and 25(OH)D did not associate. Finally, low 25(OH)D levels did not associate genetically with levels of remnant and low-density lipoprotein-cholesterol.

Conclusions:

Genetically elevated nonfasting remnant cholesterol is associated with low 25(OH)D levels, whereas genetically reduced high-density lipoprotein-cholesterol is not associated with low 25(OH)D levels. These findings suggest that low 25(OH)D levels observationally is simply a marker for elevated atherogenic lipoproteins and question a role for vitamin D supplementation in the prevention of cardiovascular disease.

Keywords:

Mendelian randomization analysis risk factors genetics vitamin D

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