1.
Effects of Genetic and Nongenetic Factors on Total and Bioavailable 25(OH)D Responses to Vitamin D Supplementation.
Yao, P, Sun, L, Lu, L, Ding, H, Chen, X, Tang, L, Xu, X, Liu, G, Hu, Y, Ma, Y, et al
The Journal of clinical endocrinology and metabolism. 2017;(1):100-110
Abstract
CONTEXT Little is known about how genetic and nongenetic factors modify responses of vitamin D supplementation in nonwhite populations. OBJECTIVE To investigate factors modifying 25-hydroxyvitamin D [25(OH)D] and bioavailable 25(OH)D [25(OH)DBio] responses after vitamin D3 supplementation. DESIGN, SETTING, PARTICIPANTS, AND INTERVENTION In this 20-week, randomized, double-blinded, placebo-controlled trial, 448 Chinese with vitamin D deficiency received 2000 IU/d vitamin D3 or placebo. MAIN OUTCOME MEASURES Serum 25(OH)D, vitamin D-binding protein (VDBP), parathyroid hormone (PTH) and calcium were measured, and 25(OH)DBio was calculated based on VDBP levels. Six common polymorphisms in vitamin D metabolism genes were genotyped. RESULTS Between-arm net changes were +30.6 ± 1.7 nmol/L for 25(OH)D, +2.7 ± 0.2 nmol/L for 25(OH)DBio, and -5.2 ± 1.2 pg/mL for PTH, corresponding to 70% [95% confidence interval (CI), 62.8% to 77.2%] net reversion rate for vitamin D deficiency at week 20 (P < 0.001). Only 25(OH)DBio change was positively associated with calcium change (P < 0.001). Genetic factors (GC-rs4588/GC-rs7041, VDR-rs2228570, and CYP2R1-rs10741657; P ≤ 0.04) showed stronger influences on 25(OH)D or 25(OH)DBio responses than nongenetic factors, including baseline value, body mass index, and sex. An inverse association of PTH-25(OH)D was demonstrated only at 25(OH)D of <50.8 (95% CI, 43.6 to 59.0) nmol/L. CONCLUSIONS Supplemented 2000 IU/d vitamin D3 raised 25(OH)D and 25(OH)DBio but was unable to correct deficiency in 25% of Chinese participants, which might be partially attributed to the effect of genetic modification. More studies are needed to elucidate appropriate vitamin D recommendations for Asians and the potential clinical implications of 25(OH)DBio.
2.
Intracellular adhesion molecule-1 K469E gene polymorphism and risk of diabetic microvascular complications: a meta-analysis.
Su, X, Chen, X, Liu, L, Chang, X, Yu, X, Sun, K
PloS one. 2013;(7):e69940
Abstract
BACKGROUND A number of studies evaluated the association of intracellular adhesion molecule-1 (ICAM-1) K469E (rs5498, A/G) gene polymorphism with diabetic microvascular complications (DMI) including diabetic nephropathy (DN) and diabetic retinopathy (DR) in different populations. However, the results of individual studies remain conflicting. METHODS A comprehensive search was conducted to identify all eligible studies of the above-mentioned associations. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were assessed using the fixed or random effect model. RESULTS Seven studies involving 3411 subjects were included. Overall, the meta-analysis showed a significant association of the A allele with increased risk of DMI susceptibility in a recessive model (OR = 1.37, 95% CI 1.04-1.80, P = 0.02). In the subgroup analysis stratified by ethnicity, significant association was found in Asians but not in Caucasians (OR = 1.78, 95% CI 1.13-2.81, P = 0.01; OR = 1.10, 95% CI 0.79-1.54, P = 0.58, respectively). Moreover, it showed a significant association between the A allele and risk of DN in a recessive model (OR = 1.25, 95% CI 1.02-1.55, P = 0.04). CONCLUSIONS This meta-analysis suggested that the K469E polymorphism in ICAM-1 gene might affect individual susceptibility to DMI and showed a discrepancy in different ethnicities. Further investigations are needed to validate the association.