Gestational diabetes mellitus and vitamin D deficiency: genetic contribution of CYP27B1 and CYP2R1 polymorphisms

Ramos-Lopez, Elizabeth; Kahles, H.; Weber, Sarah; Kukic, A.; Penna-Martinez, Marissa; Badenhoop, Klaus; Louwen, Frank

doi:10.1111/j.1463-1326.2008.00879.x

Cited by 52 publications

(17 citation statements)

References 14 publications

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“…We observed no associations between CYP27B1 SNPs and concentrations of either 25(OH)D or 1,25(OH) 2 D, in contrast to other published studies (26, 44–46). The CYP27B1 SNP most commonly reported to have a significant relationship with 25(OH)D in prior epidemiological studies is rs10877012 (26, 45, 46).…”

Section: Discussioncontrasting

confidence: 99%

“…The CYP27B1 SNP most commonly reported to have a significant relationship with 25(OH)D in prior epidemiological studies is rs10877012 (26, 45, 46). However, the direction of the association between genotypes and 25(OH)D varied between the studies, the minor allele frequency is relatively rare, and limited or no functional data are available; therefore, this variant was not selected for the present study.…”

Section: Discussionmentioning

confidence: 99%

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CYP24A1andCYP27B1Polymorphisms, Concentrations of Vitamin D Metabolites, and Odds of Colorectal Adenoma Recurrence

Hibler

Klimentidis

Jurutka

et al. 2015

Nutrition and Cancer

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Development of colorectal adenoma and cancer are associated with low circulating 25-hydroxyvitamin D (25(OH)D) levels. However, less is known regarding colorectal neoplasia risk and variation in CYP27B1 or CYP24A1, genes encoding the enzymes responsible for the synthesis and catabolism of 1α,25-hydroxyvitamin D (1,25(OH)2D). This study examined associations between CYP27B1 and CYP24A1 polymorphisms, circulating 25(OH)D and 1,25(OH)2D concentrations, and colorectal adenoma recurrence in a pooled sample from two clinical trials (n=1,188). Nominal associations were observed between increasing copies of the T allele in CYP24A1 rs927650 and 25(OH)D concentrations (p=0.02); as well as colorectal adenoma recurrence, with ORs (95% CIs) of 1.30 (0.99–1.70) and 1.38 (1.01–1.89) for heterozygotes and minor allele homozygotes, respectively (p=0.04). In addition, a statistically significant relationship between CYP24A1 rs35051736, a functional polymorphism, and odds for advanced colorectal adenoma recurrence was observed (p<0.001). Further, nominally statistically significant interactions were observed between rs2296241 and 25(OH)D as well as rs2762939 and 1,25(OH)2D (pinteraction = 0.10, respectively). Overall, CYP24A1 polymorphisms may influence the development of advanced lesions, and modify the effect of vitamin D metabolites on adenoma recurrence. Further study is necessary to characterize the differences between circulating vitamin D metabolite measurements compared to cellular level activity in relation to cancer risk.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 99%

CYP24A1andCYP27B1Polymorphisms, Concentrations of Vitamin D Metabolites, and Odds of Colorectal Adenoma Recurrence

Hibler

Klimentidis

Jurutka

et al. 2015

Nutrition and Cancer

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“…This SNP, located on chromosome 11p15.2, is in complete LD ( r 2 = 1 in the HapMap CEU samples) with rs1993116 (Supplementary Material, Fig. S3), which has been inconsistently associated with 25(OH)D levels in the literature (22,23). We confirmed a significant association between the latter SNP and vitamin D levels ( P = 1.6 × 10 −17 ) in our replication sample and found a genome-wide significance for the combined studies from meta-analysis ( P = 2.9 × 10 −17 ).…”

Section: Resultsmentioning

confidence: 99%

Genome-wide association study of circulating vitamin D levels

Ahn¹,

Yu²,

Stolzenberg-Solomon³

et al. 2010

Human Molecular Genetics

708

753

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The primary circulating form of vitamin D, 25-hydroxy-vitamin D [25(OH)D], is associated with multiple medical outcomes, including rickets, osteoporosis, multiple sclerosis and cancer. In a genome-wide association study (GWAS) of 4501 persons of European ancestry drawn from five cohorts, we identified single-nucleotide polymorphisms (SNPs) in the gene encoding group-specific component (vitamin D binding) protein, GC, on chromosome 4q12-13 that were associated with 25(OH)D concentrations: rs2282679 (P = 2.0 × 10−30), in linkage disequilibrium (LD) with rs7041, a non-synonymous SNP (D432E; P = 4.1 × 10−22) and rs1155563 (P = 3.8 × 10−25). Suggestive signals for association with 25(OH)D were also observed for SNPs in or near three other genes involved in vitamin D synthesis or activation: rs3829251 on chromosome 11q13.4 in NADSYN1 [encoding nicotinamide adenine dinucleotide (NAD) synthetase; P = 8.8 × 10−7], which was in high LD with rs1790349, located in DHCR7, the gene encoding 7-dehydrocholesterol reductase that synthesizes cholesterol from 7-dehydrocholesterol; rs6599638 in the region harboring the open-reading frame 88 (C10orf88) on chromosome 10q26.13 in the vicinity of ACADSB (acyl-Coenzyme A dehydrogenase), involved in cholesterol and vitamin D synthesis (P = 3.3 × 10−7); and rs2060793 on chromosome 11p15.2 in CYP2R1 (cytochrome P450, family 2, subfamily R, polypeptide 1, encoding a key C-25 hydroxylase that converts vitamin D3 to an active vitamin D receptor ligand; P = 1.4 × 10−5). We genotyped SNPs in these four regions in 2221 additional samples and confirmed strong genome-wide significant associations with 25(OH)D through meta-analysis with the GWAS data for GC (P = 1.8 × 10−49), NADSYN1/DHCR7 (P = 3.4 × 10−9) and CYP2R1 (P = 2.9 × 10−17), but not C10orf88 (P = 2.4 × 10−5).

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“…Based on previous studies we selected 10 SNPs located in genes coding for 25-hydroxylase/CYP2R1 (rs10741657 and rs2060793), 24-hydroxylase/CYP24A1 (rs6013897 and rs2762939), 1α-hydroxylase/CYP27B1 (rs10877012 and rs703895) and VDR (rs1544410 (Bsm1), rs731236 (Taq1), rs7975232 (Apa1), and rs2228570 (Fok1)) [21], [22], [23], [24], [25]. The nucleic acid sequences of the selected SNPs were found through the database http://snpper.chip.org/.…”

Section: Methodsmentioning

confidence: 99%

1,25-Dihydroxyvitamin D and the Vitamin D Receptor Gene Polymorphism Apa1 Influence Bone Mineral Density in Primary Hyperparathyroidism

et al. 2013

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ObjectiveParathyroid hormone (PTH) and vitamin D are the most important hormones regulating calcium metabolism. In primary hyperparathyroidism (PHPT) excessive amounts of PTH are produced. Bone turnover is enhanced, leading to reduced bone mineral density and elevated levels of serum calcium. The aim of this study was to investigate relations between serum levels of 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)2D) and bone mineral density, as well as known genetic polymorphisms in the vitamin D receptor and enzymes metabolising vitamin D in patients with PHPT.Design/SubjectsWe conducted a cross-sectional study of 52 patients with PHPT.ResultsMean level of 25(OH)D was 58.2 nmol/L and median 1,25(OH)2D level was 157 pmol/L. Among our patients with PHPT 36.5% had 25(OH)D levels below 50 nmol/L. Serum 1,25(OH)2D was inversely correlated to bone mineral density in distal radius (p = 0.002), but not to bone mineral density at lumbar spine or femoral neck. The vitamin D receptor polymorphism Apa1 (rs7975232) was associated with bone mineral density in the lumbar spine.ConclusionsThe results suggest that PHPT patients with high blood concentrations of 1,25(OH)2D may have the most deleterious skeletal effects. Randomized, prospective studies are necessary to elucidate whether vitamin D supplementation additionally increases serum 1,25(OH)2D and possibly enhances the adverse effects on the skeleton in patients with PHPT.

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Gestational diabetes mellitus and vitamin D deficiency: genetic contribution of CYP27B1 and CYP2R1 polymorphisms

Cited by 52 publications

References 14 publications

CYP24A1andCYP27B1Polymorphisms, Concentrations of Vitamin D Metabolites, and Odds of Colorectal Adenoma Recurrence

CYP24A1andCYP27B1Polymorphisms, Concentrations of Vitamin D Metabolites, and Odds of Colorectal Adenoma Recurrence

Genome-wide association study of circulating vitamin D levels

1,25-Dihydroxyvitamin D and the Vitamin D Receptor Gene Polymorphism Apa1 Influence Bone Mineral Density in Primary Hyperparathyroidism

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