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Maternal and Newborn Vitamin D-Binding Protein, Vitamin D Levels, Vitamin D Receptor Genotype, and Childhood Type 1 Diabetes.

ABSTRACT: OBJECTIVE:Circumstantial evidence links 25-hydroxy vitamin D [25(OH)D], vitamin D-binding protein (DBP), vitamin D-associated genes, and type 1 diabetes (T1D), but no studies have jointly analyzed these. We aimed to investigate whether DBP levels during pregnancy or at birth were associated with offspring T1D and whether vitamin D pathway genetic variants modified associations between DBP, 25(OH)D, and T1D. RESEARCH DESIGN AND METHODS:From a cohort of >100,000 mother/child pairs, we analyzed 189 pairs where the child later developed T1D and 576 random control pairs. We measured 25(OH)D using liquid chromatography-tandem mass spectrometry, and DBP using polyclonal radioimmunoassay, in cord blood and maternal plasma samples collected at delivery and midpregnancy. We genotyped mother and child for variants in or near genes involved in vitamin D metabolism (GC, DHCR7, CYP2R1, CYP24A1, CYP27B1, and VDR). Logistic regression was used to estimate odds ratios (ORs) adjusted for potential confounders. RESULTS:Higher maternal DBP levels at delivery, but not in other samples, were associated with lower offspring T1D risk (OR 0.86 [95% CI 0.74-0.98] per ?mol/L increase). Higher cord blood 25(OH)D levels were associated with lower T1D risk (OR = 0.87 [95% CI 0.77-0.98] per 10 nmol/L increase) in children carrying the VDR rs11568820 G/G genotype (P interaction = 0.01 between 25(OH)D level and rs11568820). We did not detect other gene-environment interactions. CONCLUSIONS:Higher maternal DBP level at delivery may decrease offspring T1D risk. Increased 25(OH)D levels at birth may decrease T1D risk, depending on VDR genotype. These findings should be replicated in other studies. Future studies of vitamin D and T1D should include VDR genotype and DBP levels.

SUBMITTER: Tapia G

PROVIDER: S-EPMC6905492 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Maternal and Newborn Vitamin D-Binding Protein, Vitamin D Levels, Vitamin D Receptor Genotype, and Childhood Type 1 Diabetes.

Tapia German G Mårild Karl K Dahl Sandra R SR Lund-Blix Nicolai A NA Viken Marte K MK Lie Benedicte A BA Njølstad Pål R PR Joner Geir G Skrivarhaug Torild T Cohen Arieh S AS Størdal Ketil K Stene Lars C LC

Diabetes care 20190128 4

<h4>Objective</h4>Circumstantial evidence links 25-hydroxy vitamin D [25(OH)D], vitamin D-binding protein (DBP), vitamin D-associated genes, and type 1 diabetes (T1D), but no studies have jointly analyzed these. We aimed to investigate whether DBP levels during pregnancy or at birth were associated with offspring T1D and whether vitamin D pathway genetic variants modified associations between DBP, 25(OH)D, and T1D.<h4>Research design and methods</h4>From a cohort of >100,000 mother/child pairs, ...[more]

PMID: 30692241

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Project description:ObjectivePrevious studies have noted a specific association between type 1 diabetes and insufficient levels of vitamin D, as well as polymorphisms within genes related to vitamin D pathways. Here, we examined whether serum levels or genotypes of the vitamin D-binding protein (VDBP), a molecule key to the biologic actions of vitamin D, specifically associate with the disorder.Research design and methodsA retrospective, cross-sectional analysis of VDBP levels used samples from 472 individuals of similar age and sex distribution, including 153 control subjects, 203 patients with type 1 diabetes, and 116 first-degree relatives of type 1 diabetic patients. Single nucleotide polymorphism (SNP) typing for VDBP polymorphisms (SNP rs4588 and rs7041) was performed on this cohort to determine potential genetic correlations. In addition, SNP analysis of a second sample set of banked DNA samples from 1,502 type 1 diabetic patients and 1,880 control subjects also was used to determine genotype frequencies.ResultsSerum VDBP levels were highest in healthy control subjects (median 423.5 µg/mL [range 193.5-4,345.0; interquartile range 354.1-]586), intermediate in first-degree relatives (402.9 µg/mL [204.7-4,850.0; 329.6-492.4]), and lowest in type 1 diabetic patients (385.3 µg/mL [99.3-1,305.0; 328.3-473.0]; P = 0.003 vs. control subjects). VDBP levels did not associate with serum vitamin D levels, age, or disease duration. However, VDBP levels were, overall, lower in male subjects (374.7 µg/mL [188.9-1,602.0; 326.9-449.9]) than female subjects (433.4 µg/mL [99.3-4,850.0; 359.4-567.8]; P < 0.0001). It is noteworthy that no differences in genotype frequencies of the VDBP polymorphisms were associated with serum VDBP levels or between type 1 diabetic patients and control subjects.ConclusionsSerum VDBP levels are decreased in those with type 1 diabetes. These studies suggest that multiple components in the metabolic pathway of vitamin D may be altered in type 1 diabetes and, collectively, have the potential to influence disease pathogenesis.

Project description:IntroductionPrenatal smoking exposure may lead to permanent changes in neonatal inflammation and immune response that have lifelong implications, including increased risks for atopy and respiratory disorders.MethodsThe effect of maternal smoking on neonatal biomarkers of inflammation and immune response was assessed among 3459 singletons and twins in the Upstate KIDS Study. The following inflammatory biomarkers were measured using newborn dried blood spots (DBSs): interleukin (IL)-1?, IL-1 receptor antagonist, IL-6, IL-8, C-reactive protein, and tumor necrosis factor alpha. Immunoglobulins (IgE, IgA, IgM, and IgG subclasses) were also assessed. We used generalized estimating equations to calculate mean differences (?) in biomarker levels by timing of pregnancy smoking, cigarette load, and secondhand smoke exposure after adjusting for sociodemographic and lifestyle factors including maternal body mass index.ResultsOf the 344 (12%) women reporting smoking during pregnancy, about 40% continued throughout pregnancy and 13% reported smoking more than 1 pack per day. After covariate adjustment and Bonferroni correction for multiple comparisons, maternal smoking throughout pregnancy remained significantly associated with increased levels of IL-8 (? = 0.20, 95% confidence interval: 0.07, 0.32; p < .003). No significant associations were found with cigarette load or secondhand smoke exposure. Higher IgG3 levels were also associated with maternal smoking throughout pregnancy, although the association became nominally significant after adjustment for covariates (? = 0.09; 95% confidence interval: 0.0007, 0.17; p < .05).ConclusionsMaternal smoking throughout pregnancy was independently associated with increased IL-8 levels in newborns. Importantly, neonates of women who stopped smoking anytime in pregnancy did not have increased IL-8 levels.ImplicationsThis study evaluated a range of inflammatory biomarkers and immunoglobulins in association with maternal smoking and timing/duration of smoking along with secondhand smoke exposure. By using DBSs, we present data from a large cohort of children born in Upstate New York. Our findings suggest that early differences in immunoregulation of neonates exposed to maternal smoking for full duration in utero may already be detected at birth.

Project description:Genetic polymorphisms affect lipid profiles and are associated with disease complications. Genetic variants in the vitamin D receptor (VDR) gene are associated with type 2 diabetes mellitus (T2DM). In this study, we investigated the effects of VDR genotypes on the lipid profile and disease complications of T2DM patients in a Jordanian population. Ninety T2DM patients were genotyped for four major functional VDR genetic variants, rs2228570 C > T (FokI), rs7975232 A > C (ApaI), rs731236 T > C (TaqI), and rs1544410 C > T (BsmI), using the polymerase chain reaction−restriction fragment length polymorphism method. Lipid profiles and diabetes complications were analyzed and correlated with VDR genotypes. We found that the VDR rs7975232 and rs1544410 alleles were significantly (p = 0.008−0.04) associated with high-density lipoprotein (HDL) levels and retinopathy among patients. Carriers of the rs7975232 A/A genotype exhibited higher levels (49.68 ± 15.86 mg/dL) of HDL than patients with the A/C (44.73 ± 13.38 mg/dL) and C/C (37.93 ± 9.22 mg/dL) genotypes. Moreover, carriers of the rs1544410 T/T genotype had higher levels of HDL (54.31 ± 16.45 mg/dL) than patients with the C/T (43.57 ± 13.24 mg/dL) and C/C (43.98 ± 13.17 mg/dL) genotypes. T2DM patients who carry the rs7975232 C/C genotype were at higher risk (odds ratio [OR] = 7.88) of developing retinopathy compared with carriers of the rs7975232 C/A and A/A genotypes. In addition, T2DM patients with the rs1544410 C/C genotype had a higher risk (OR = 4.21) of developing retinopathy than patients with the rs1544410 C/T and T/T genotypes. Therefore, we concluded that the VDR rs7975232 and rs1544410 alleles were associated with HDL levels and retinopathy and can be considered as potential genetic biomarkers for the lipid profile and retinopathy complication among T2DM patients in a Jordanian population of Arabic origin. Further studies with larger sample sizes are needed to confirm our findings.

Dataset Information

Maternal and Newborn Vitamin D-Binding Protein, Vitamin D Levels, Vitamin D Receptor Genotype, and Childhood Type 1 Diabetes.

Publications

Maternal and Newborn Vitamin D-Binding Protein, Vitamin D Levels, Vitamin D Receptor Genotype, and Childhood Type 1 Diabetes.

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