Vitamin D Receptor Fok-I Polymorphism Modulates Diabetic Host Response to Vitamin D Intake

Abstract

OBJECTIVEInterpopulation as well as interindividual variations in response to vitamin D intake commonly observed in subjects with type 2 diabetes may be related to genetic makeup. One of the candidate genes potentially responsible for this diversity is vitamin D receptor (VDR). This study aimed to investigate the interactive effect of VDR Fok-I polymorphism and vitamin D intake on diverse aspects of diabetic host response.RESEARCH DESIGN AND METHODSGlycemic status, lipid profiles, inflammatory biomarkers, and VDR Fok-I genotypes were determined in diabetic subjects (n = 140) who participated in a randomized controlled trial. Participants consumed two 250-mL bottles per day of yogurt drink (doogh) fortified with 500 IU vitamin D/250 mL for 12 weeks.RESULTSMean serum 25(OH)D increased by ~30 nmol/L (P < 0.001). The time × intervention effect was significant for 25(OH)D (P = 0.030), HDL (P = 0.011), high-sensitivity C-reactive protein (hsCRP) (P < 0.001), interleukin (IL)-4 (P = 0.008), and IL-6 (P = 0.017) among the genotypic groups. The alleles were defined as ‘‘F’’ or ‘‘f’’ depending on the absence or presence of the restriction site, respectively. The least increment in 25(OH)D was in ff (23.0 ± 3.8 nmol/L) compared with Ff (31.2 ± 3.4 nmol/L) and FF (35.6 ± 2.7 nmol/L) (P for trend = 0.009), but only the difference between ff and FF was significant (P = 0.023). FF group had the largest decrement of both hsCRP and IL-6 compared with Ff (P < 0.001 and P = 0.038) and ff (P = 0.010 and P = 0.048), respectively.CONCLUSIONSWe concluded that those of VDR ff genotype may be regarded as “low responders” to vitamin D intake in terms of response of circulating 25(OH)D and certain inflammatory biomarkers. A nutrigenetic approach may, therefore, be needed to protect diabetic patients from vitamin D deficiency.

Vitamin D, Oxidative Stress and Diabetes

“…We found that VDR FokI ff were 'low-responders' to vitamin D in terms of rise in circulating 25(OH)D and amelioration of some inflammatory markers, including highly sensitive C-reactive protein (hsCRP) and IL-6 [48]. However, further analyses revealed no between-group difference in changes of TAC, MDA, GSH, SOD and GSH-Px among VDR FokI genotypes.…”

“…While the recent recommended dietary allowance (RDA) for vitamin D has been increased to 600 IU (from a previously recommended dosage of 400 IU), most experts still believe this amount would be insufficient to make desirable serum levels of 25(OH)D of 75-100 nmol/L, so they recommend a daily intake of 400-1000 IU/d for children under 1y, 600-1000 IU/d for children 1-18y, and 1500-2000 IU/d for adults [5]. The requirement in diabetic carriers of certain genotypic variants (like VDR FokI ff) may prove to be even higher [48]. The method of determination of circulating 25(OH)D is another issue of concern.…”

Genetic and acquired factors influencing the effectiveness and toxicity of drug therapy in osteoporosis

“…A genome-wide study revealed that allelic variants of several genes involved in vitamin D metabolism and transport are associated with serum levels of 25-hydroxyvitamin D [60 ] . Some, but not all, candidate gene studies also found associations between genetic variants and the response to vitamin D supplements, and more research is needed to clarify this issue [61][62][63][64] .…”

Association of a VDR Gene Polymorphism with Risk of Colorectal Cancer in Kashmir

“…If the initiating translation starts from this alternative site (thymine variant), it results in the generation of a longer VDR protein of 427 amino acids (Kostner et al, 2009). The polymorphisms in this area have been studied singly and in combination with other polymorphisms of VDR in a number of malignant and non malignant conditions (Chiu et al, 2001;Malecki et al, 2003;Park et al, 2006;Kadyska et al, 2007;Hubner et al, 2008;Neyestani et al, 2013).…”