Genetic and Environmental Determinants of 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D Levels in Hispanic and African Americans

Engelman, Corinne D.; Fingerlin, Tasha E.; Langefeld, Carl D.; Hicks, Pamela J.; Rich, Stephen S.; Wagenknecht, Lynne E.; Bowden, Donald W.; Norris, Jill M.

doi:10.1210/jc.2007-2702

Cited by 234 publications

(249 citation statements)

References 21 publications

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“…Gender, age, presence of diabetes mellitus, smoking status, blood pressure, total cholesterol, and HDL cholesterol were included in the model because they were identified as classical cardiovascular risk factors (23). In addition, blood pressure, BMI, and 25(OH)D were included in the model because these variables might mediate the relationship between VDR genotypes and mortality whereas these variables are associated with both VDR genotypes (8,9,(24)(25)(26) and mortality (27,28).…”

Section: Discussionmentioning

confidence: 99%

Associations between vitamin D receptor genotypes and mortality in a cohort of older Dutch individuals

Jongh

Lips

Rijs

et al. 2011

European Journal of Endocrinology

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Context: Vitamin D receptor (VDR) polymorphisms are associated with a variety of diseases, which may translate into an effect on mortality. Objective: To investigate the associations between VDR gene variants and mortality among older people. Design: The analyses were conducted in a population-based, prospective cohort of the Longitudinal Aging Study Amsterdam. Adequate DNA analysis was performed in 923 men and women (R65 years). We aimed to assess the associations between mortality and the VDR polymorphism FokI, three haplotypes of the Cdx2 and GATA polymorphisms, and three haplotypes of the BsmI, ApaI, and TaqI polymorphisms. Results: During the median follow-up of 10.7 years, 480 participants deceased (51%). Homozygosity for the Cdx2-GATA haplotype 1 allele was associated with a 30% higher mortality risk compared to the absence of alleles (hazard ratios (HR) 1.30, 95% confidence intervals (CI) 1.01-1.68). Adjustment for cardiovascular risk factors and 25-hydroxyvitamin D levels did not affect this HR. The number of copies of the Cdx2-GATA haplotype 1 allele was associated, although not significantly, with an increased risk of osteoporotic fractures (0 copiesZreference, HR, 95% CI: 1 copy 2.01, 0.99-4.07 and 2 copies 1.81, 0.87-4.18). After adjustment for osteoporotic fractures, homozygosity for the Cdx2-GATA haplotype 1 allele was no longer associated with higher mortality risk (HR 1.08, 95% CI 0.83-1.41).

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Section: Discussionmentioning

confidence: 99%

Associations between vitamin D receptor genotypes and mortality in a cohort of older Dutch individuals

Jongh

Lips

Rijs

et al. 2011

European Journal of Endocrinology

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“…The protein isoforms corresponding to these haplotypes are thought to have variable binding affinity for vitamin D metabolites, Gc1F having the highest and Gc2 the lowest (37). Carriage of GC1F is more common in African Americans and in groups originating from areas with higher sun exposure (38), whereas carriage of GC1S is more common in those with origins farther from the equator (39,40). GC2 has been associated repeatedly with lower 25(OH)D levels in genome-wide variation studies (38,41,42), as well as in children (43).…”

Section: Low Serum Concentrations Of Total 25-hydroxyvitamin D (25[oh]d)mentioning

confidence: 99%

“…Repeat genotyping was performed on 5% of the samples, and negative controls were performed on DNA-free samples, SNPs with success rate ,96% were excluded. Haplotypes were assigned on the basis of genotyping results for the SNPs rs4588 and rs7041 (38,41). Deviations from HardyWeinberg were tested using the x 2 test.…”

Section: Genotyping Cohort and Bioavailable Vitamin Dmentioning

confidence: 99%

Critically Ill Children Have Low Vitamin D Binding Protein, Influencing Bioavailability of Vitamin D

Madden¹,

Feldman²,

Chun³

et al. 2015

Annals ATS

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Rationale: Vitamin D deficiency, often defined by total serum 25-hydroxyvitamin D (25[OH]D) ,20 ng/ml, is common in critically ill patients, with associations with increased mortality and morbidity in the intensive care unit. Correction of vitamin D deficiency in critical illness has been recommended, and ongoing clinical trials are investigating the effect of repletion on patient outcome. The biologically active amount of 25(OH)D depends on the concentration and protein isoform of vitamin D-binding protein (VDBP), which is also an acutephase reactant affected by inflammation and injury.Objectives: We performed a secondary analysis of a cohort of critically ill children in which we reported a high rate of vitamin D deficiency, to examine how VDBP level and genotype would impact vitamin D status. Methods:We prospectively enrolled 511 children admitted to the pediatric intensive care unit over a 12-month period. Measurements and Main Results:We measured serum VDBP in 479 children. We genotyped single nucleotide polymorphisms rs7041 and rs4588 in the VDBP gene (GC) to determine haplotypes GC1F, GC1S, and GC2 in 178 subjects who consented, then calculated bioavailable 25(OH)D from serum 25(OH)D, VDBP, albumin, and GC haplotype. The median serum VDBP level was 159 mg/ml (interquartile range, 108-221), lower than has been reported in healthy children. Factors predicting lower levels in multivariate analysis included age ,1 year, nonwhite race, being previously healthy, 25(OH)D ,20 ng/ml and greater illness severity. In the subgroup that was genotyped, GC haplotype had the strongest association with VDBP level; carriage of one additional copy of GC1S was associated with a 37.5% higher level (95% confidence interval, 31.9-44.8; P , 0.001). Bioavailable 25(OH)D was also inversely associated with illness severity (r = 20.24, P , 0.001), and ratio to measured total 25(OH)D was variable and related to haplotype.Conclusions: Physiologic deficiency of 25(OH)D in critical illness may be more difficult to diagnose, given that lower VDBP levels increase bioavailability. Treatment studies conducted on the basis of total 25(OH)D level, without consideration of VDBP concentration and genotype, may increase the risk of falsely negative results.

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“…We selected polymorphisms that have been reported to be associated with serum 25(OH)D levels in either GWAS or candidate gene studies [8,9,11,12,[15][16][17][18][19][20]. Well-known VDR polymorphisms reported to be associated with bone mineral density and several vitamin D-related diseases were also included [21][22][23].…”

Section: Gene Analysismentioning

confidence: 99%

Association of vitamin D-related gene polymorphisms with manifestation of vitamin D deficiency in children

et al. 2012

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Genetic and Environmental Determinants of 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D Levels in Hispanic and African Americans

Abstract: SNPs in the DBP are associated with levels of 25(OH)D and 1,25(OH)2D in HA and AA participants in the Insulin Resistance Atherosclerosis Family Study.

Cited by 234 publications

References 21 publications

Associations between vitamin D receptor genotypes and mortality in a cohort of older Dutch individuals

Associations between vitamin D receptor genotypes and mortality in a cohort of older Dutch individuals

Critically Ill Children Have Low Vitamin D Binding Protein, Influencing Bioavailability of Vitamin D

Association of vitamin D-related gene polymorphisms with manifestation of vitamin D deficiency in children

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