Genetic Influences on Vitamin D Status and Forearm Fracture Risk in African American Children

Ryan, Leticia Manning; Chamberlain, James M.; Singer, Steven A.; Wood, Rachel E.; Tosi, Laura L.; Freishtat, Robert J.; Gordish‐Dressman, Heather; Teach, Stephen J.; Devaney, Joseph M.

doi:10.2310/jim.0b013e3182567e2a

Cited by 5 publications

(2 citation statements)

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“…It is well recognized that individuals with darker skin pigmentation living at higher latitudes tend to have lower 25(OH)D. This may in part reflect clustering of genotypes within ethnic groups. For example, the G allele at rs12785878 ( DHCR7 ) is typically more prevalent in nonwhite populations ( 25 – 29 ). Although our study included only women of white ethnicity, the G allele was associated with lower baseline 25(OH)D. The greater prevalence of the G allele at rs12785878 with a resulting increase in 7-DHC reductase activity (either due to a functional modification or increased synthesis) leading to reduced availability of 7-DHC for conversion to previtamin D might contribute to lower 25(OH)D in individuals with darker skin pigmentation.…”

Section: Discussionmentioning

confidence: 99%

Response to Antenatal Cholecalciferol Supplementation Is Associated With Common Vitamin D–Related Genetic Variants

Moon

Harvey

Cooper

et al. 2017

The Journal of Clinical Endocrinology &Amp; Metabolism

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Context:Single-nucleotide polymorphisms (SNPs) in genes related to vitamin D metabolism have been associated with serum 25-hydroxyvitamin D [25(OH)D] concentration, but these relationships have not been examined following antenatal cholecalciferol supplementation.Objective:To determine whether SNPs in DHCR7, CYP2R1, CYP24A1, and GC are associated with the response to gestational cholecalciferol supplementation.Design:Within-randomization group analysis of the Maternal Vitamin D Osteoporosis Study trial of antenatal cholecalciferol supplementation.Setting:Hospital antenatal clinics.Participants:In total, 682 women of white ethnicity (351 placebo, 331 cholecalciferol) were included. SNPs at rs12785878 (DHCR7), rs10741657 (CYP2R1), rs6013897 (CYP24A1), and rs2282679 (GC) were genotyped.Interventions:1000 IU/d cholecalciferol from 14 weeks of gestation until delivery.Main Outcome Measure:25(OH)D at randomization and 34 weeks of gestation were measured in a single batch (Liaison; Diasorin, Dartford, UK). Associations between 25(OH)D and the SNPs were assessed by linear regression using an additive model [β represents the change in 25(OH)D per additional common allele].Results:Only rs12785878 (DHCR7) was associated with baseline 25(OH)D [β = 3.1 nmol/L; 95% confidence interval (CI), 1.0 to 5.2 nmol/L; P < 0.004]. In contrast, rs10741657 (CYP2R1) (β = −5.2 nmol/L; 95% CI, −8.2 to −2.2 nmol/L; P = 0.001) and rs2282679 (GC) (β = 4.2 nmol/L; 95% CI, 0.9 to 7.5 nmol/L; P = 0.01) were associated with achieved 25(OH)D status following supplementation, whereas rs12785878 and rs6013897 (CYP24A1) were not.Conclusions:Genetic variation in DHCR7, which encodes 7-dehyrocholesterol reductase in the epidermal vitamin D biosynthesis pathway, appears to modify baseline 25(OH)D. In contrast, the response to antenatal cholecalciferol supplementation was associated with SNPs in CYP2R1, which may alter 25-hydroxylase activity, and GC, which may affect vitamin D binding protein synthesis or metabolite affinity.

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Section: Discussionmentioning

confidence: 99%

Response to Antenatal Cholecalciferol Supplementation Is Associated With Common Vitamin D–Related Genetic Variants

Moon

Harvey

Cooper

et al. 2017

The Journal of Clinical Endocrinology &Amp; Metabolism

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“…of African Americans have insufficient serum levels of 25-hydroxyvitamin D [2]. These data may explain the author Ryan L. M.'s interest in the association between fractures of African American children and low levels of 25-hydroxyvitamin D in their studies [28][29][30][31]. It is also emphasized that dark pigmentation of the skin is considered a risk factor for low levels of 25-hydroxyvitamin D due to a reduced ability to produce this vitamin in the skin [38].…”

Section: Discussionmentioning

confidence: 99%

Implications of Vitamin D Status for Children’s Bone Health: A Data Mining Analyses of Observational Studies

Martins,

Arrepia,

Jural

et al. 2024

Pesqui. Bras. Odontopediatria Clín. Integr.

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Objective: To investigate associations/correlations between bone alterations and vitamin D status in children through data mining analyses based on observational studies. Material and Methods: Searches in PubMed, Scopus, Web of Science, and Embase databases were performed to recover studies, published until October 2022, with healthy children, which investigated the vitamin D status, related or not to undesirable bone alterations linked to bone quality (bone mineral density and bone mineral content), fracture or anthropometry. Country, study design, area of expertise (medicine, nutrition, dentistry, others), bone outcome, 25-hydroxyvitamin D data (serum or intake levels), the exams for bone diagnosis, and the results were analyzed in the VantagePoint TM software. Results: Of 20,583 studies, 27 were included. The USA (n=9; 33.3%) had the highest number of publications. Cross-sectional (n=11; 40.7%), case-control (n=9; 33.3%), and cohort studies (n=7; 25.9%) contemplated the medicine and nutritional areas without any study in dentistry. Studies about bone quality (n=21; 77.8%), analyzed through dual-energy X-ray absorptiometry (DXA; n=14; 51.8%), with association (n=16; 59.2%) between the low serum levels of 25-hydroxyvitamin D and undesirable bone alterations (n=14; 51.8%) were the most prevalent. Conclusion: Most studies were conducted in the medical area and showed an association between low bone quality and low levels of 25-hydroxyvitamin D, verified through DXA.

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The associations of 25-hydroxyvitamin D levels, vitamin D binding protein gene polymorphisms, and race with risk of incident fracture-related hospitalization: Twenty-year follow-up in a bi-ethnic cohort (the ARIC Study)

Takiar

Lutsey

Zhao

et al. 2015

Bone

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Background Deficient levels of 25-hydroxyvitamin D [25(OH)D] have been associated with increased fracture risk. Racial differences in fracture risk may be related to differences in bioavailable vitamin D due to single nucleotide polymorphism (SNP) variations in the Vitamin D Binding Protein (DBP). Methods We measured 25(OH)D levels in 12,781 middle-aged white and black participants [mean age 57 years (SD 5.7), 25% black] in the ARIC Study who attended the second examination from 1990–1992. Participants were genotyped for two DBP SNPs (rs4588 and rs7041). Incident hospitalized fractures were measured by abstracting hospital records for ICD-9 codes. We used Cox proportional hazards models to evaluate the association between 25(OH)D levels and risk of fracture with adjustment for possible confounders. Interactions were tested by race and DBP genotype. Results There were 1,122 incident fracture-related hospitalizations including 267 hip fractures over a median of 19.6 years of follow-up. Participants with deficient 25(OH)D (<20 ng/ml) had a higher risk of any fracture hospitalization [HR=1.21 (95% CI 1.05–1.39)] and hospitalization for hip fracture [HR=1.35 (1.02–1.79)]. No significant racial interaction was noted (p-interaction=0.20 for any fracture; 0.74 for hip fracture). There was no independent association of rs4588 and rs7041 with fracture. However, there was a marginal interaction for 25(OH)D deficiency with rs7041 among whites (p-interaction=0.065). Whites with both 25(OH)D deficiency and the GG genotype [i.e. with predicted higher levels of DBP and lower bioavailable vitamin D] were at the greatest risk for any fracture [HR=1.48 (1.10–2.00)] compared to whites with the TT genotype and replete 25(OH)D (reference group). Conclusions Deficient 25(OH)D levels are associated with higher incidence of hospitalized fractures. Marginal effects were seen in whites for the DBP genotype associated with lower bioavailable vitamin D, but results inconclusive. Further investigation is needed to more directly evaluate the association between bioavailable vitamin D and fracture risk.

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Genetic Influences on Vitamin D Status and Forearm Fracture Risk in African American Children

Cited by 5 publications

References 28 publications

Response to Antenatal Cholecalciferol Supplementation Is Associated With Common Vitamin D–Related Genetic Variants

Response to Antenatal Cholecalciferol Supplementation Is Associated With Common Vitamin D–Related Genetic Variants

Implications of Vitamin D Status for Children’s Bone Health: A Data Mining Analyses of Observational Studies

The associations of 25-hydroxyvitamin D levels, vitamin D binding protein gene polymorphisms, and race with risk of incident fracture-related hospitalization: Twenty-year follow-up in a bi-ethnic cohort (the ARIC Study)

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