Evidence of a casual relationship between vitamin D deficiency and hypertension: a family-based study.

An association between vitamin D deficiency and hypertension has been observed in numerous studies. However, blood pressure improvements resulting from supplementation with vitamin D have been inconsistent. The causal relationship between vitamin D deficiency and hypertension is still unclear and was investigated in this family-based study. A total of 1370 individuals from both vitamin D deficiency and hypertension families were included. First, the heritability of vitamin D deficiency was estimated by the Falconer method. Second, SNPs (single nucleotide polymorphisms) of vitamin D metabolic and functional pathway genes associated with vitamin D deficiency were screened by a family-based association test, and the findings were further verified in nuclear families with vitamin D deficiency. Finally, a family-based association test was applied to investigate the association between selected SNPs associated with vitamin D deficiency and hypertension. The heritability of vitamin D deficiency was 50.4% in this family-based study. Allele C of rs3847987 was a risk factor for vitamin D deficiency (OR: 1.639, 95% CI: 1.170-2.297, P = 0.004). Furthermore, a family-based association of rs3847987 with hypertension was found in both additive and recessive models (P < 0.05). In addition, vitamin D deficiency was associated with hypertension (OR: 1.317, 95% CI: 1.022-1.698, P = 0.033). In conclusion, rs3847987 in the VDR gene was associated with both vitamin D deficiency and hypertension. Therefore, vitamin D deficiency may be a causal factor for hypertension.

Effect of Vitamin D on Blood Pressure and Hypertension in the General Population: An Update Meta-Analysis of Cohort Studies and Randomized Controlled Trials.

BACKGROUND: The effect of vitamin D supplementation on blood pressure has been explored in previous meta-analyses, but whether the association is causal in the general population is still unknown. We evaluated the association comprehensively and quantitatively. METHODS: We searched PubMed and Embase for relevant cohort studies and randomized controlled trials (RCTs). We used a 2-step generalized least-squares method to assess the dose-response association of circulating 25-hydroxyvitamin D (25[OH]D) and hypertension and a fixed-effects model to pool the weighted mean differences (WMDs) and corresponding 95% confidence intervals (95% CIs) of blood pressure across RCTs. RESULTS: We identified 11 cohort studies and 27 RCTs, with 43,320 and 3,810 participants, respectively. The dose-response relationship between circulating 25(OH)D levels and hypertension risk was approximately L-shaped (Pnonlinearity = .04), suggesting that the risk of hypertension increased substantially below 75 nmol/L as 25(OH)D decreased, but it remained significant over the range of 75-130 nmol/L. However, pooled results of RCTs showed that there was no significant reduction in systolic blood pressure (WMD, -0.00 mm Hg; 95% CI, -0.71 to 0.71) or diastolic blood pressure (WMD, 0.19 mm Hg; 95% CI, -0.29 to 0.67) after vitamin D intervention. CONCLUSIONS: The results of this meta-analysis indicate that supplementation with vitamin D does not lower blood pressure in the general population. RCTs with long-term interventions and a sufficient number of participants who have low levels of vitamin D are needed to validate these findings.

Epigenetic-Based Biomarkers in the Malignant Transformation of BEAS-2B Cells Induced by Coal Tar Pitch Extract.

Background and objectives: The carcinogenicity of coal tar pitch (CTP) to occupational workers has been confirmed by the International Agency for Research on Cancer, especially for lung cancer. Herein, we explored the dynamic changes of epigenetic modifications in the malignant transformation process of CTP-induced BEAS-2B cells and also provided clues for screening early biomarkers of CTP-associated occupational lung cancer. Methods: BEAS-2B cells treated with 3.0 µg/mL CTP extract (CTPE) were cultured to the 30th passage to set up a malignant transformation model, which was confirmed by platelet clone formation assay and xenograft assay. DNA methylation levels were determined by ultraviolet-high performance liquid chromatography. mRNA levels in cells and protein levels in supernatants were respectively detected by Real-Time PCR and enzyme-linked immunosorbent assay. Results: The number of clones and the ability of tumor formation in nude mice of CTPE-exposed BEAS-2B cells at 30th passage were significantly increased compared to vehicle control. Moreover, genomic DNA methylation level was down-regulated. The mRNA levels of DNMT1, DNMT3a and HDAC1 as well as the expression of DNMT1 protein were up-regulated since the 10th passage. From the 20th passage, the transcriptional levels of DNMT3b, let-7a and the expression of DNMT3a, DNMT3b, and HDAC1 proteins were detected to be higher than vehicle control, while the level of miR-21 increased only at the 30th passage. Conclusion: Data in this study indicated that the changes of epigenetic molecules including DNMT1, DNMT3a, DNMT3b, HDAC1, and let-7a occurred at the early stages of BEAS-2B cell malignant transformation after CTPE exposure, which provided critical information for screening early biomarkers of CTP-associated occupational lung cancer.

Associations of CYP24A1 copy number variation with vitamin D deficiency and insulin secretion.

Vitamin D plays an important role in insulin secretion. As the enzyme that initiates degradation of the active metabolite of vitamin D (1,25-(OH)2 vitamin D), 24-hydroxylase encoded by CYP24A1 may be associated with insulin secretion. In this study, we aimed at investigating the association between copy number of CYP24A1 and the concentration of insulin. Included in the study were 1528 rural people from Henan Province of China. The copy number of CYP24A1 and the concentrations of serum 25(OH) vitamin D3 and insulin were determined. Association between copy number of CYP24A1 and vitamin D deficiency was investigated with logistic regression model. Correlation between copy number of CYP24A1 and serum insulin was observed by Spearman correlation. The results suggested that copy number variation of CYP24A1 was associated with vitamin D deficiency. Higher copy number of CYP24A1 was a risk factor for vitamin D deficiency (adjusted odds ratio: 1.199; 95% confidence interval: 1.028-1.397; P = 0.021). Furthermore, copy number of CYP24A1 was positive correlated with the concentration of serum insulin (r = 0.115; P < 0.001), regardless of vitamin D status, age, and body mass index (BMI). Increased copy number of CYP24A1 is associated with not only vitamin D deficiency but also increased serum insulin. Vitamin D supplement may be beneficial to individuals with high copy number of CYP24A1. Novelty Increased copy number of CYP24A1 was a risk factor of vitamin D deficiency. Increased copy number of CYP24A1 was associated with increased serum concentration of insulin independent of age, BMI, and vitamin D status.

Effect of vitamin D supplementation on fasting plasma glucose, insulin resistance and prevention of type 2 diabetes mellitus in non-diabetics: A systematic review and meta-analysis.

Increasing epidemiological studies suggest that there is an association between vitamin D deficiency and risk of type 2 diabetes mellitus (T2DM). Therefore, randomized clinical trials (RCTs) have been performed to observe the effect of vitamin D supplementation on preventing T2DM, decreasing fasting plasma glucose (FPG) and improving insulin resistance to confirm the association between vitamin D and T2DM. However, the results of RCTs on controlling FPG level, improving insulin resistance and preventing T2DM in non-diabetics are inconsistent. In the present study, a systematic meta-analysis considering individual variation and intervention strategy was conducted to establish an objective and definitive conclusion. The results suggested that vitamin D supplementation had no significant effect on controlling FPG level, improving insulin resistance or preventing T2DM in non-diabetics in a pooled meta-analysis of 23 articles (containing 28 RCTs). However, stratified analysis indicated that supplementation of vitamin D had differential effects on FPG control, insulin sensitivity improvement and T2DM prevention in individuals with different baseline states: FPG was decreased for those with BMI <25 (P=0.048) or 20≤ 25(OH)D <30 ng/ml (P=0.002); insulin resistance was improved for those with 25(OH)D ≥30 ng/ml (P=0.021); and risk of T2DM was lower for pre-diabetic individuals (P=0.047) or for those with 25≤ BMI <30 (P=0.032). Additionally, the effect on T2DM prevention was improved when the supplement dose was >2,000 IU/day (P=0.047) and with intervention without calcium (P=0.047). Thus, further trials should focus on individual baselines and the supplementation strategy of vitamin D in the prevention of T2DM.