A vitamin D pathway gene gene interaction affects low density lipoprotein cholesterol levels.
Much evidence suggests an association between vitamin D deficiency and chronic diseases such as obesity and dyslipidemia. Although genetic factors play an important role in the etiology of these diseases, only a few studies have investigated the relationship between vitamin D related genes and anthropometric and lipid profiles. The aim of this study was to investigate the association of three vitamin D related genes with anthropometric and lipid parameters in 542 adult individuals. We analyzed the rs2228570 polymorphism in the vitamin D receptor gene (VDR) rs2134095 in the retinoid X receptor gamma gene (RXRG) and rs7041 in the vitamin D binding protein gene (GC) Polymorphisms were genotyped by TaqMan allelic discrimination. Gene gene interactions were evaluated by the general linear model. The functionality of the polymorphisms was investigated using the following predictors and databases: SIFT (Sorting Intolerant from Tolerant) PolyPhen 2 (Polymorphism Phenotyping v2) and Human Splicing Finder 3. We identified a significant effect of the interaction between RXRG (rs2134095) and GC (rs7041) on low density lipoprotein cholesterol (LDL c) levels (P=.005) Furthermore, our in silico analysis suggested a functional role for both variants in the regulation of the gene products. Our results suggest that the vitamin D related genes RXRG and GC affect LDL c levels. These findings are in agreement with other studies that consistently associate vitamin D and lipid profile. Together, our results corroborate the idea that analyzing gene gene interaction would be helpful to clarify the genetic component of lipid profile.
The Journal of nutritional biochemistry