Genes such as CYP27B1, CYP24A1 and Vitamin D – JAMA Nov 2012

Genetic Variants and Associations of 25-Hydroxyvitamin D Concentrations With Major Clinical Outcomes

JAMA. 2012;308(18):1898-1905. doi:10.1001/jama.2012.17304.
Gregory P. Levin, PhD; Cassianne Robinson-Cohen, PhD; Ian H. de Boer, MD, MS; Denise K. Houston, PhD; Kurt Lohman, MS; Yongmei Liu, PhD; Stephen B. Kritchevsky, PhD; Jane A. Cauley, DrPh; Toshiko Tanaka, PhD; Luigi Ferrucci, MD, PhD; Stefania Bandinelli, MD; Kushang V. Patel, PhD, MPH; Emil Hagström, MD, PhD; Karl Michaëlsson, MD, PhD; Håkan Melhus, MD, PhD; Thomas Wang, MD; Myles Wolf, MD, MMSc; Bruce M. Psaty, MD, PhD; David Siscovick, MD, MPH; Bryan Kestenbaum, MD, MS

Context Lower serum 25-hydroxyvitamin D concentrations are associated with greater risks of many chronic diseases across large, prospective community-based studies. Substrate 25-hydroxyvitamin D must be converted to 1,25-dihydroxyvitamin D for full biological activity, and complex metabolic pathways suggest that interindividual variability in vitamin D metabolism may alter the clinical consequences of measured serum 25-hydroxyvitamin D.

Objective To investigate whether common variation within genes encoding the

• vitamin D–binding protein,
• megalin, cubilin,
• CYP27B1,
• CYP24A1, and the
• vitamin D receptor (VDR)

modify associations of low 25-hydroxyvitamin D with major clinical outcomes.

Design, Setting, and Participants Examination of 141 single-nucleotide polymorphisms in a discovery cohort of 1514 white participants (who were recruited from 4 US regions) from the community-based Cardiovascular Health Study. Participants had serum 25-hydroxyvitamin D measurements in 1992-1993 and were followed up for a median of 11 years (through 2006). Replication meta-analyses were conducted across the independent, community-based US Health, Aging, and Body Composition (n = 922; follow-up: 1998-1999 through 2005), Italian Invecchiare in Chianti (n = 835; follow-up: 1998-2000 through 2006), and Swedish Uppsala Longitudinal Study of Adult Men (n = 970; follow-up: 1991-1995 through 2008) cohort studies.

Main Outcome Measure Composite outcome of incident hip facture, myocardial infarction, cancer, and mortality over long-term follow-up.

Results Interactions between 5 single-nucleotide polymorphisms and low 25-hydroxyvitamin D concentration were identified in the discovery phase and 1 involving a variant in the VDR gene replicated in independent meta-analysis. Among Cardiovascular Health Study participants, low 25-hydroxyvitamin D concentration was associated with hazard ratios for risk of the composite outcome of 1.40 (95% CI, 1.12-1.74) for those who had 1 minor allele at rs7968585 and 1.82 (95% CI, 1.31-2.54) for those with 2 minor alleles at rs7968585. In contrast, there was no evidence of an association (estimated hazard ratio, 0.93 [95% CI, 0.70-1.24]) among participants who had 0 minor alleles at this single-nucleotide polymorphism.

Conclusion Known associations of low 25-hydroxyvitamin D with major health outcomes may vary according to common genetic differences in the vitamin D receptor.

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See also Vitamin D Life

• Colon cancer 30 percent more likely if problems with Vitamin D genes CYP24A1 or CYP27B1 – Nov 2015
• All items in Genetics and vitamin D 266 items
• 35 items in CYP27B1 category
• CYP24A1 enzyme and Vitamin D
• CYP24A1 gene in cancer cells may actually deactivate vitamin D – Oct 2012
• Mice lacking CYP2R1 enzyme activate about half of much vitamin D – Sept 2013
• CLICK HERE to use Google to find CYP24A1 in Vitamin D Life - 1350 hits as of May 2019
• CYP24A1 gene mutation is a cause of some infant vitamin D toxicity – Aug 2011 NEJM
• Breast cancer and Vitamin D receptors, CP27B1, and CYP24A1 – Sept 2010
• Genes May Play a Role in Vitamin D Deficiency – June 2010
• Genome-wide association study of circulating vitamin D levels -May 2010
• Genetics Determines Vit D Response - vitamin D council March 2010
• 360X more bacterial than human genes in the body – June 2012
• Vitamin D levels are strongly associated with genes: overview of twin studies – Nov 2012
• GC and CYP2R1 genes associated with higher summer vitamin D levels – Jan 2013
• Obese have 50 percent less of two enzymes in fatty tissue to process vitamin D – May 2013
• 229 Genes related to vitamin D - Aug 2010 which contains the following graph

• Hypertension 3.1 X more likely in males with poor CPY24A1 gene (but 2.5 X less likely for females) – May 2019

See also web

• Vitamin D Gene Changes May Drive Disease MedPageToday
  "The totality of these findings suggests that low 25(OH)D concentration may be a modifiable risk factor for many chronic diseases,”