Vitamin D binding protein is a key determinant of 25-hydroxyvitamin D levels in infants and toddlers
Bibliographic record
Abstract
Circulating 25-hydroxyvitamin D (25-OHD) levels vary among human populations. Only limited information regarding determinants of these measures is available for infants and children, particularly in minority groups at greatest risk for vitamin D deficiency. We identified demographic determinants of circulating 25-OHD in a large cohort of minority children, and now extend our studies to examine potential roles of vitamin D binding protein (DBP) as a determinant of 25-OHD levels. Serum DBP level and common single nucleotide polymorphisms (SNPs) at positions 432 and 436 in the GC gene, encoding DBP, were examined. We confirmed self-reported ancestry using ancestry informative markers (AIMs), and included quantitative AIMs scores in the analysis. The multivariate model incorporated previously identified demographic and nutritional determinants of 25-OHD in this cohort, as well as GC SNPs and circulating DBP. Genetic variants in GC differed by self-reported ancestry. The 1f allele (D432/T436) was enriched in African Americans, occurring in 71%. Homozygosity for the 1f allele (DDTT) occurred in 53% of African Americans but only 6% of Caucasians and 13% of Hispanics. Circulating DBP was significantly correlated with 25-OHD. GC SNPs were associated with both circulating DBP and 25-OHD. It appears that progressive substitution of lysine for threonine at the 436 position results in lower circulating 25-OHD. Multivariate analysis revealed that genetic variance in GC significantly contributes to circulating DBP as well as 25-OHD. Moreover, the effect of GC SNPs on 25-OHD are evident after adjusting for their effects on circulating DBP. Thus in young children genetic variance of the common GC T436K SNP affects circulating levels of the DBP protein, which in turn affects circulating 25-OHD. However, the GC genotype also affects circulating 25-OHD independently of its effect on circulating DBP. These findings provide data that may be important in the interpretation of vitamin D status in children of varying ancestral backgrounds.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".