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

Need for a nutrigenetic approach

Diabetes Care November 16, 2012

Tirang R. Neyestani, PHD1⇓, Abolghassem Djazayery, PHD2, Sakineh Shab-Bidar, MSC2, Mohammad Reza Eshraghian, PHD3, Ali Kalayi, BSC1, Nastaran Shariátzadeh, BSC1, Niloufar Khalaji, MSC1, Malihe Zahedirad, MSC1, A’zam Gharavi, BSC1, Anahita Houshiarrad, MSC1, Maryam Chamari, MSC2 and Sepideh Asadzadeh, BSC1

1 Department of Nutrition Research, National Nutrition and Food Technology Research Institute, and Faculty of Nutrition Science and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran

2 Department of Nutrition and Biochemistry, School of Public Health and Institute of Public Health Research, Tehran University of Medical Sciences, Tehran, Iran

3 Department of Biostatistics and Epidemiology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

Corresponding author: Tirang R. Neyestani, [email protected] [email protected].

OBJECTIVE Interpopulation 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 METHODS Glycemic status, lipid profiles, inflammatory biomarkers, and VDR Fok-qI 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.

RESULTS Mean 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),

• hsCRP (P < 0.001),

• 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.

CONCLUSIONS We 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.

Received May 16, 2012. Accepted August 28, 2012. © 2012 by the American Diabetes Association.

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Summary by Vitamin D Life

140 diabetics were given 1000 IU vitamin D (not much) daily in RCT

Those having Fok-I gene ff were designated as “low responders”, having just 9.2 ng response

Those having Fok-I gene FF had 14.2 ng response

Average vitamin D 12 ng response

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