Vitamin D binding protein polymorphisms significantly impact vitamin D status in children.
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ABSTRACT: Background
Polymorphic alleles of the vitamin D (vitD)-binding protein (VDBP) gene are associated with discriminatory differences in circulating concentrations of 25-hydroxyvitamin D (25-D), the indicator of vitD status (sufficiency defined by the Endocrine Society as ≥75 nmol/L). Within a diverse group of children, we hypothesized that reaching recommended daily allowance (RDA) of vitD intake would have differential impact on vitD status depending on VDBP variability.Methods
VDBP alleles (Gc1S, Gc1F, Gc2) in 123 children (1-4 annual visits/child; ages 1-8 years) were compared for relationships with serum 25-D concentrations and daily vitD intake.Results
In African-American children, reaching the vitD RDA was associated with significantly higher mean serum 25-D concentrations for the 20% carrying the VDBP 1S allele than for the large majority without this allele (77 vs. 61 nmol/L 25-D; p = 0.038). Children with the Gc1S/1S homozygous genotype (30% Caucasians, 24% Hispanics, 2% African-Americans) who met RDA had 51% (39 nmol/L) greater mean serum 25-D than those below RDA (p < 0.0001).Conclusions
VDBP genetic variability was a significant factor affecting childhood vitD status when following RDA guidelines. This study may inform public health policy of uniformity in recommended childhood vitD dosage, especially regarding racially/ethnically associated disparities.
SUBMITTER: Newton DA
PROVIDER: S-EPMC6677641 | biostudies-literature |
REPOSITORIES: biostudies-literature
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| S-EPMC7861048 | biostudies-literature
Project description:Abstract The study aimed to determine the influence of DBP gene polymorphisms in vitamin D metabolites before and after vitamin D supplementation. Out of 234 participants (126 females and 108 males), 146 had vitamin D deficiency (25(OH)D <50nmol/l) and were given 2000IU daily dose of vitamin D for 12 months. Two common single nucleotide polymorphisms (SNPs), (rs4588 and rs7041) of the DBP gene were assessed. Post supplementation median 25(OH)D was significantly higher [61.2 (46.3-76.8) and 66.6 (53.2-83.7)] in participants with CC genotype of rs4588 and GG genotype of rs7041 than other genotypes (p<0.001). Participants with T allele are 2.9 (1.9-4.5) times more likely to be a non-responder (unable to achieve serum 25(OH)D post-supplementation) than those with G allele (p<0.001). Participants with A allele are 3.7 (2.1-6.6) times more likely to be a non-responder than those with C allele (p<0.001). Furthermore, participants with TT and TG are 6.2 and 4.2 times more likely to be a non-responder than those with the GG genotype (p-values <0.001) even after adjustments for age, gender, BMI, baseline 25(OH)D concentration and other alleles. Participants with AA and CA genotypes are 12.4 (1.4-110) and 4.1 (2.1-8.0) times more likely to be non-responders as compared to those with CC genotype but lost significance after adjustment. The SNPs, rs7041 and rs4588 variants of the DBP gene are associated with baseline 25(OH)D levels and modifies 25(OH)D response after vitamin D supplementation in Saudi adults.
| S-EPMC6552145 | biostudies-literature
Project description:BACKGROUND:Low levels of total 25-hydroxyvitamin D are common among black Americans. Vitamin D-binding protein has not been considered in the assessment of vitamin D deficiency. METHODS:In the Healthy Aging in Neighborhoods of Diversity across the Life Span cohort of blacks and whites (2085 participants), we measured levels of total 25-hydroxyvitamin D, vitamin D-binding protein, and parathyroid hormone as well as bone mineral density (BMD). We genotyped study participants for two common polymorphisms in the vitamin D-binding protein gene (rs7041 and rs4588). We estimated levels of bioavailable 25-hydroxyvitamin D in homozygous participants. RESULTS:Mean (±SE) levels of both total 25-hydroxyvitamin D and vitamin D-binding protein were lower in blacks than in whites (total 25-hydroxyvitamin D, 15.6±0.2 ng per milliliter vs. 25.8±0.4 ng per milliliter, P<0.001; vitamin D-binding protein, 168±3 ?g per milliliter vs. 337±5 ?g per milliliter, P<0.001). Genetic polymorphisms independently appeared to explain 79.4% and 9.9% of the variation in levels of vitamin D-binding protein and total 25-hydroxyvitamin D, respectively. BMD was higher in blacks than in whites (1.05±0.01 g per square centimeter vs. 0.94±0.01 g per square centimeter, P<0.001). Levels of parathyroid hormone increased with decreasing levels of total or bioavailable 25-hydroxyvitamin D (P<0.001 for both relationships), yet within each quintile of parathyroid hormone concentration, blacks had significantly lower levels of total 25-hydroxyvitamin D than whites. Among homozygous participants, blacks and whites had similar levels of bioavailable 25-hydroxyvitamin D overall (2.9±0.1 ng per milliliter and 3.1±0.1 ng per milliliter, respectively; P=0.71) and within quintiles of parathyroid hormone concentration. CONCLUSIONS:Community-dwelling black Americans, as compared with whites, had low levels of total 25-hydroxyvitamin D and vitamin D-binding protein, resulting in similar concentrations of estimated bioavailable 25-hydroxyvitamin D. Racial differences in the prevalence of common genetic polymorphisms provide a likely explanation for this observation. (Funded by the National Institute on Aging and others.).
| S-EPMC4030388 | biostudies-literature
Project description:BackgroundVitamin D-binding protein (DBP) may alter the biological activity of total 25-hydroxyvitamin D [25(OH)D]; this could influence on the effects of vitamin D in relation to bone mineral density (BMD) and fractures. Emerging data suggest that fetuin-A may be involved in bone metabolism. We aimed to investigate the influence of DBP gene polymorphism on the relationship of vitamin D status and fetuin-A levels to BMD and bone markers.MethodsThis cross-sectional study was part of a health survey of employees of the Electricity Generating Authority of Thailand (1,734 healthy subjects, 72% male). Fasting blood samples were assayed for 25(OH)D, fetuin-A, N-terminal propeptides of type 1 procollagen (P1NP), C-terminal cross-linking telopeptides of type I collagen (CTx-I), and DBP rs2282679 genotypes. L1-L4 lumbar spine and femoral BMD were measured using dual-energy X-ray absorptiometry.ResultsThe DBP rs2282679 genotype distribution conformed to the Hardy-Weinberg equilibrium. There were no correlations between 25(OH)D levels and BMD and bone markers. But a trend of positive correlation was observed for the DBP genotypes with total hip BMD, and for the interaction between 25(OH)D and DBP genotypes with BMD at all femoral sites. We further analyzed data according to DBP genotypes. Only in subjects with the AA (common) genotype, 25(OH)D levels were positively related to BMD and bone markers, while fetuin-A was negatively related to total hip BMD, independently of age, gender and BMI.ConclusionsThe interaction between vitamin D status, as measured by circulating 25(OH)D and DBP rs2282679 genotypes, modified the association between 25(OH)D and BMD and bone markers. Differences in DBP genotypes additionally influenced the correlation of fetuin-A levels with femoral BMD.
| S-EPMC4389666 | biostudies-literature
Project description: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 acute-phase 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 ?g/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?=?-0.24, 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.
| S-EPMC5467088 | biostudies-literature
Project description:Vitamin D deficiency has adverse effects on renal allograft outcomes, and polymorphisms of genes encoding vitamin D-binding protein (VDBP) and vitamin D receptor (VDR) are defined to play a role in these conditions. The goal of the current investigation was to evaluate the connection between those polymorphisms with acute rejection, viral infection history, and recipients' vitamin D status. In this study, 115 kidney transplant recipients and 100 healthy individuals were included. VDR polymorphisms including FokI (rs2228570), Apal (rs7975232), BsmI (rs1544410), as well as VDBP (rs7040) polymorphisms were studied using high resolution melting (PCR-HRM) analysis among the studied groups. The frequency of G allele in Apal rs7975232 polymorphism in the kidney transplant recipients was 0.63 times lower than healthy individuals (p = 0.026). Further, the G allele frequency in VDBP rs7040 polymorphism was significantly lower in patients with allograft rejection (p = 0.002). Considering the incidence of viral infection, significant differences were identified between the frequencies of VDR FokI (OR = 2.035; 95% CI 1.06-2.89, p = 0.030) and VDBP rs7040 (OR = 0.40; 95% CI 0.24-0.67, p < 0.001) T alleles in the studied groups. Moreover, the VDBP rs7040 GG genotype distribution was low in the recipients with a history of viral infection (p = 0.004). VDR (FokI) and VDBP (rs7040) alleles and their genotype distribution are significantly associated with allograft outcomes including allograft rejection and viral infection in the studied population.
| S-EPMC8067077 | biostudies-literature
Project description:PurposeEpidemiologic evidence indicates that time outdoors reduces the risk of myopia, suggesting a possible role for vitamin D. This case-control study was conducted to determine whether single-nucleotide polymorphisms (SNPs) within VDR at 12q13.11 and GC at 4q12-13 are associated with myopia.MethodsThe primary analysis was conducted on 81 white adult control subjects between 18 and 50 years of age with a spherical equivalent refractive error between +0.50 and +2.00 D in both eyes and less than 1.50 D of astigmatism. Affected myopic subjects were 289 unrelated white adults at least 18 years of age with at least -0.75 D myopia in both principal meridians of both eyes.ResultsOne SNP within VDR was significantly associated with myopia in the multivariate analysis of the primary sample (rs2853559: odds ratio = 1.99, P = 0.003). In a subsample of less severely myopic white subjects between -0.75 and -4.00 D, three SNPs within VDR were significantly associated in a multivariate model after adjustment for multiple comparisons (rs2239182: odds ratio = 2.17, P = 0.007; rs3819545: odds ratio = 2.34, P = 0.003; rs2853559: odds ratio = 2.14, P = 0.0035), accounting for 12% of model variance over age alone.ConclusionsPolymorphisms within VDR appear to be associated with low to moderate amounts of myopia in white subjects. Future studies should determine whether this finding can be replicated and should explore the biological significance of these variations with respect to myopia.
| S-EPMC3109057 | biostudies-literature
Project description:Blacks have different dominant polymorphisms in the vitamin D-binding protein (DBP) gene that result in higher bioavailable vitamin D than whites. This study tested whether the lack of association between 25-hydroxyvitamin D (25OHD) and multiple sclerosis (MS) risk in blacks and Hispanics is due to differences in these common polymorphisms (rs7041, rs4588). We recruited incident MS cases and controls (blacks 116 cases/131 controls; Hispanics 183/197; whites 247/267) from Kaiser Permanente Southern California. AA is the dominant rs7041 genotype in blacks (70.0%) whereas C is the dominant allele in whites (79.0% AC/CC) and Hispanics (77.1%). Higher 25OHD levels were associated with a lower risk of MS in whites who carried at least one copy of the C allele but not AA carriers. No association was found in Hispanics or blacks regardless of genotype. Higher ultraviolet radiation exposure was associated with a lower risk of MS in blacks (OR = 0.06), Hispanics and whites who carried at least one copy of the C allele but not in others. Racial/ethnic variations in bioavailable vitamin D do not explain the lack of association between 25OHD and MS in blacks and Hispanics. These findings further challenge the biological plausibility of vitamin D deficiency as causal for MS.
| S-EPMC5852760 | biostudies-literature
Project description:BackgroundIn chronic obstructive pulmonary disease (COPD), the blood vitamin D3 level is generally low, and genetic polymorphisms of vitamin D-binding protein encoded by the GC gene are associated with COPD development. In this study, we examined the relationship between GC polymorphisms and plasma vitamin D3 level in Korean patients with COPD.MethodsThe study included 175 COPD patients from the Korean Obstructive Lung Disease Cohort. Multivariate analysis was conducted with adjustment for age, body mass index (BMI), lung function, smoking status, smoking amount, and seasonal variation in blood vitamin D level. Vitamin D deficiency was defined as a plasma 25-hydroxyvitamin D3 level lower than 20 ng/mL.ResultsThe mean plasma vitamin D3 level was 17.5 ng/mL. The GC1F variant (44.3%) and genotype 1F-2 (27.4%) were the most common. The plasma vitamin D3 level was lower in patients with the GC2 variant (estimated =-3.73 ng/mL) and higher in those with genotype 1F-1S (estimated =4.08 ng/mL). The GC2 variant was a significant risk factor for vitamin D deficiency (odds ratio =2.41). Among COPD clinical parameters, vitamin D deficiency was associated with a lower ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) regardless of GC polymorphisms. FEV1/FVC was higher in patients with genotype 1F-1F (estimated =3.61%) and lower in those with genotype 1F-2 (estimated =-3.31%). The 6-minute walking distance was shorter for patients with the GC1F variant (estimated =-38.91 m) and longer for those with the GC2 variant (estimated =26.98 m). The emphysema index was higher for patients with the GC1S variant (estimated =6.56%) and genotype 1F-1S (estimated =9.86%), regardless of the vitamin D level.ConclusionThe GC2 variant is a risk factor for vitamin D deficiency, and genotype 1F-1S is a protective factor against vitamin D deficiency. GC polymorphisms and vitamin D deficiency correlate with clinical outcomes for Korean patients with COPD.
| S-EPMC4827885 | biostudies-literature
Project description:ContextLower 25-hydroxyvitamin D (25(OH)D) levels have consistently been associated with higher mortality among participants with colorectal cancer (CRC).ObjectiveTo investigate whether the association between 25(OH)D and CRC mortality differs according to vitamin D binding protein (also known as Gc) isoforms.MethodsWe examined the association between prediagnostic 25(OH)D levels and overall and CRC-specific mortality among participants with CRC within 2 prospective US cohorts. Cox proportional hazards regression was used to estimate the hazard ratios (HRs) and 95% CIs.Results588 participants with CRC were observed until the date of death or last follow-up (2018), whichever came first. Deficient vs sufficient 25(OH)D concentrations (<30 vs ≥50 nmol/L) were associated with higher overall mortality (HR 2.06; 95% CI 1.34-3.18) but not with CRC-specific mortality (HR 1.51; 95% CI 0.75-3.07). The HRs for overall mortality comparing deficient vs sufficient concentrations were 2.43 (95% CI 1.26-4.70) for those with the Gc1-1 isoform (rs4588 CC) and 1.63 (95% CI 0.88-3.02) for those with the Gc1-2 or Gc2-2 (rs4588 CA or AA) isoform (P for interaction = .54). The HRs for CRC-specific mortality were 1.18 (95% CI 0.27-5.14) for those with the Gc1-1 isoform and 1.41 (95% CI 0.62-3.24) for those with the Gc1-2 or Gc2-2 isoform (P for interaction = .94).ConclusionIn these 2 US cohorts, we found that lower 25(OH)D levels were associated with higher overall mortality, but this association did not differ by Gc isoforms.
| S-EPMC10188303 | biostudies-literature