CYP2R1 polymorphisms are important modulators of circulating 25-hydroxyvitamin D levels in elderly females with vitamin insufficiency, but not of the response to vitamin D supplementation
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Authors
Arabi, Asma
Khoueiry-Zgheib, Nathalie
Awada, Zainab
Mahfouz, Rami A.R.
Al-Shaar, Laila
Hoteit, M.
Rahme, Maya
Baddoura, Rafic M.
Halabi, Gazi K.
Singh, Ravinder Jit
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Volume Title
Publisher
Springer London
Abstract
Summary: We studied the association between CYP2R1 genetic polymorphisms and circulating 25-hydroxyvitamin D [25(OH)D] before and after supplementation with vitamin D3 in 218 elderly. We found differences between 3 and 8 ng/ml in circulating levels at baseline in women but not in the response after 1 year of supplementation. Introduction: This study evaluated the association between polymorphisms in four single nucleotide polymorphisms (SNPs) of the CYP2R1 gene and 25(OH)D levels before and 1 year after supplementation with two different doses of vitamin D3 (600 IU daily or a dose equivalent to 3750 IU daily), in a cohort of 218 (96 men and 122 women) Lebanese elderly overweight subjects. Methods: Genotyping was performed for rs12794714, rs10741657, rs1562902, and rs10766197 SNPs using real-time PCR. The 25(OH)D levels were measured by liquid chromatography tandem mass spectrometry. Results: At baseline, the mean ± SD age was 71.0 ± 4.7 years, BMI 30.3 ± 4.6 kg/m2, and 25(OH)D level was 20.5 ± 7.6 ng/ml. There were significant differences in mean 25(OH)D levels between genotypes in women, but not in men. After adjustment for age, season, and BMI, the homozygous for the low frequency gene variant (HLV) of rs1562902 and rs10741657 SNPs had the highest mean 25(OH)D levels with difference of 7.6 ng/ml for rs1562902 SNP (p < 0.01) and of 5.9 ng/ml for rs10741657 (p = 0.05) compared to the homozygous for the major polymorphisms (HMPs). Conversely, for rs10766197 and rs12794714 SNPs, HMP had the highest mean 25(OH)D levels with difference of 6 ng/ml for rs10766197 (p = 0.003) and of 4.8 ng/ml (p = 0.02) for rs12794714, compared to the HLV. CYP2R1 genetic polymorphisms explained 4.8 to 9.8 % of variability in 25(OH)D in women. After 1 year, there was no difference in the response to vitamin D3 supplementation between genotypes in either gender. Conclusion: This study showed a difference in 25(OH)D levels between CYP2R1 genotypes that equates a daily supplementation of 400–800 IU vitamin D, depending on genotype. It underscores possible important genetic contributions for the high prevalence of hypovitaminosis D in the Middle East. © 2016, International Osteoporosis Foundation and National Osteoporosis Foundation.
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Keywords
25(oh) vitamin d, Cyp2r1, Genetic polymorphisms, Metabolic pathway, Vitamin d supplementation, Aged, Cholecalciferol, Cholestanetriol 26-monooxygenase, Cytochrome p450 family 2, Dietary supplements, Double-blind method, Female, Genetic predisposition to disease, Genotype, Humans, Male, Polymorphism, single nucleotide, Seasons, Vitamin d, Vitamin d deficiency, 25 hydroxyvitamin d, Calcium, Colecalciferol, Cytochrome p450, Cytochrome p450 2r1, Placebo, Unclassified drug, 25-hydroxyvitamin d, Cholestanetriol 26 monooxygenase, Cyp2r1 protein, human, Aging, Article, Cohort analysis, Controlled study, Double blind procedure, Drug dose comparison, Drug megadose, Gene expression, Gene frequency, Genetic association, Genetic variability, Genotyping technique, Homozygosity, Human, Lebanese, Liquid chromatography, Low drug dose, Major clinical study, Multicenter study, Obesity, Osteoporosis, Priority journal, Randomized controlled trial, Real time polymerase chain reaction, Sex difference, Single nucleotide polymorphism, Tandem mass spectrometry, Treatment duration, Treatment response, Vitamin deficiency, Vitamin supplementation, Analogs and derivatives, Blood, Dietary supplement, Genetic predisposition, Genetics, Season