Association between the genetic variant in the vitamin D pathway (rs2282679), circulating 25-hydroxyvitamin D levels, insulin resistance and metabolic syndrome criteria / Asociación entre la variante genética en la vía de la vitamina D (rs2282679), niveles circulantes de 25-hidroxivitamina D, resistencia a la insulina y criterios de síndrome metabólico

Background and aims: some studies have reported links between 25-hydroxyvitamin D levels and the presence of metabolic syndrome. The aim of the present study was to evaluate whether an association exists among 25-hydroxyvitamin D, rs2282679 of the GC gene and metabolic syndrome (MS). Methods: the study involved a population of 134 postmenopausal obese females. Measurements of anthropometric parameters, blood pressure, bone turnover markers, fasting blood glucose, insulin resistance (HOMA-IR), lipid profile, C-reactive protein and prevalence of MS were recorded. Genotype of CG gene polymorphism (rs2282679) was evaluated. Results: insulin (delta: 4.6 ± 0.9 mUI/l; p = 0.02), triglycerides (delta: 21.6 ± 2.9 mg/dl; p = 0.04) and HOMA-IR (delta: 1.1 ± 0.9 unit; p = 0.02) were lower in TT subjects than TG + GG patients. The percentages of individuals who had MS (OR = 2.80, 95 % CI = 1.39-5.65; p = 0.02), hypertriglyceridemia (OR = 2.39, 95 % CI = 1.44-5.96; p = 0.01), and hyperglycemia (OR = 2.72, 95 % CI = 1.23-6.00; p = 0.43) were higher in G allele carriers. Logistic regression analysis showed an increased risk of MS in G allele carriers (OR = 2.36, 95 % CI = 1.11-5.91, p = 0.02) and an increased risk of 25-hydroxyvitamin D deficiency (< 20 ng/ml) (OR = 2.43, 95 % CI = 1.13-6.69, p = 0.02), too. Conclusions: a negative association among G allele and insulin resistance, hypertriglyceridemia, deficiency of 25 hydroxyvitamin D levels and MS was reported in this population. (AU)

Antecedentes y objetivos: algunos estudios han demostrado una relación entre los niveles de 25-hidroxivitamina D y la presencia del síndrome metabólico. El objetivo de este estudio fue evaluar si existe una asociación entre la 25-hidroxivitamina D, la variante rs2282679 del gen GC y el síndrome metabólico (SM). Métodos: el estudio involucró a una población de 134 mujeres obesas posmenopáusicas. Se registraron parámetros antropométricos, presión arterial, marcadores de recambio óseo, glucemia en ayunas, resistencia a la insulina (HOMA-IR), perfil lipídico, proteína C reactiva y prevalencia de SM. Se evaluó el genotipo del polimorfismo del gen CG (rs2282679). Resultados: los niveles de insulina (delta: 4,6 ± 0,9 mUI/l; p = 0.02), triglicéridos (delta: 21,6 ± 2,9 mg/dl; p = 0,04) y HOMA-IR (delta: 1,1 ± 0,9 unidades; p = 0,02) fueron menores en los sujetos TT que en los pacientes TG + GG. Los porcentajes de individuos que tenían SM (OR = 2,80, IC 95 % = 1,39-5,65; p = 0,02), hipertrigliceridemia (OR = 2,39, IC 95 % = 1,44-5,96; p = 0,01) e hiperglucemia (OR = 2,72, IC 95 % = 1,23-6,00; p = 0,43) fueron mayores en los portadores del alelo G. El análisis de regresión logística mostró un mayor riesgo de SM en los portadores del alelo G (OR = 2,36, IC 95 % = 1,11-5,91; p = 0,02) y un mayor riesgo de deficiencia de 25-hidroxivitamina D (< 20 ng/ml) (OR = 2,43, IC 95 % = 1,13-6,69; p = 0,02). Conclusiones: en esta población hemos detectado una asociación negativa entre el alelo G y la resistencia a la insulina, hipertrigliceridemia, deficiencia niveles de 25-hidroxivitamina D y SM. (AU)

Calcium Homeostasis and Psychiatric Disorders: A Mendelian Randomization Study.

Observational studies have investigated the impact of calcium homeostasis on psychiatric disorders; however, the causality of associations is yet to be established. Bidirectional Mendelian randomization (MR) analysis of calcium homeostasis hormones was conducted on nine psychiatric disorders. Calcium, serum 25-hydroxyvitamin D levels (25OHD), parathyroid hormone, and fibroblast growth factor 23 are the major calcium homeostasis hormones. The causality was evaluated by the inverse variance weighted method (IVW) and the MR Steiger test, while Cochran's Q test, the MR-Egger intercept test, funnel plot, and the leave-one-out method were used for sensitivity analyses. Bonferroni correction was used to determine the causative association features (p < 6.94 × 10-4). Schizophrenia (SCZ) was significantly associated with decreased 25OHD concentrations with an estimated effect of -0.0164 (Prandom-effect IVW = 2.39 × 10-7). In the Multivariable MR (MVMR) analysis adjusting for potentially confounding traits including body mass index, obesity, mineral supplements (calcium, fish oil, and vitamin D) and outdoor time (winter and summer), the relationship between SCZ and 25OHD remained. The genetically predicted autism spectrum disorder and bipolar disorder were also nominally associated with decreased 25OHD. This study provided evidence for a causal effect of psychiatric disorders on calcium homeostasis. The clinical monitoring of 25OHD levels in patients with psychiatric disorders is beneficial.

Associations of 25-hydroxyvitamin D status and vitamin D supplementation use with mortality due to 18 frequent cancer types in the UK Biobank cohort.

BACKGROUND: Although the associations of serum 25-hydroxyvitamin D (25(OH)D) levels and vitamin D supplementation with total cancer mortality are well-known, evidence regarding the association of 25(OH)D and cancer site-specific mortality is predominantly limited to common cancer types, and most studies on vitamin D supplementation use have limitations on sample size and the adjustment of important confounding factors. METHODS: We used cause-specific Cox regression models adjusted for 48 covariates to assess the associations of vitamin D deficiency, insufficiency, and vitamin D supplementation use with mortality from any cancer and 18 specific cancers in 411,436 United Kingdom Biobank participants, aged 40-69 years. RESULTS: The majority of the study population had either vitamin D deficiency (21.1%) or insufficiency (34.4%). Furthermore, 4.1% and 20.3% of the participants regularly took vitamin D or multivitamin supplements, respectively. During a median follow-up of 12.7 years, vitamin D deficiency was associated with significantly increased mortality from total cancer and four specific cancers: stomach (hazard ratio, 95% confidence interval: 1.42, 1.05-1.92), colorectal (1.27, 1.07-1.50), lung (1.24, 1.10-1.40), and prostate (1.36, 1.06-1.75). Vitamin D insufficiency was associated with increased colorectal (1.14, 1.00-1.30) and lung cancer mortality (1.19, 1.08-1.32). Compared to non-users, vitamin D use was associated with lower lung cancer (0.75, 0.60-0.95) and total cancer mortality. Multivitamin use was associated with lower mortality from melanoma (0.64, 0.43-0.97). CONCLUSION: Vitamin D deficiency and insufficiency were associated with increased mortality from multiple common cancers. The potential to reduce cancer mortality by vitamin D supplementation in populations with low 25(OH)D levels should be further explored.

Analysis of serum levels L-arginine and 25-hydroxyvitamin D as a predictor of survival of severe preeclampsia mothers.

OBJECTIVE: This study aimed to analyze serum levels of L-arginine and 25-hydroxyvitamin D as predictors of survival in severely preeclamptic women. METHODS: This study is a retrospective descriptive study using medical record data from June to August 2019 and has received a recommendation for ethical approval with the protocol number UH20070290. The study was conducted in 4 hospitals in Makassar: Dr. General Hospital. Wahidin Sudirohusodo, Hasanuddin University Teaching Hospital, Siti Fatimah Regional Mother and Child Health Hospital, and Sitti Khadijah 1 Mother and Child Hospital. The samples of this study were mothers who gave birth with a diagnosis of normal pregnant women, severe preeclampsia, and severe preeclampsia with complications. RESULTS: Serum l-arginine level did not affect the survival of severe preeclamptic mothers. It was shown at p-value 0.799>0.05. Meanwhile, serum levels of 25-hydroxyvitamin D affect the predictors of maternal preeclampsia where the p-value is 0.024<0.05. In comparing serum levels of L-arginine and 25-hydroxyvitamin D, there was no significant difference in groups of normal pregnant women, severe preeclampsia, and severe preeclampsia with complications. CONCLUSION: Serum level of 25-hydroxyvitamin affects the survival of severe preeclamptic mothers.

The impact of serum 25-hydroxyvitamin D, calcium, and parathyroid hormone levels on the risk of coronary artery disease in patients with diabetes: a Mendelian randomization study.

BACKGROUND: To investigate the causal association between serum 25-hydroxyvitamin D (25OHD), calcium (Ca), and parathyroid hormone (PTH) levels and the risk of coronary artery disease (CAD) in patients with diabetes using a Mendelian randomization approach. METHODS: Genetic signatures associated with serum 25OHD, Ca, and PTH levels were extracted from recently published genome-wide association study (GWAS), including 79,366, 39,400, 29,155 individuals, respectively. Genetic association estimates for CAD in patients with diabetes were obtained from a GWAS of 15,666 individuals with diabetes (3,968 CAD cases, 11,696 controls). The inverse-variance-weighted method was employed for the primary analysis, and other robust methods were applied for sensitivity analyses. RESULTS: Six, seven and five single nucleotide polymorphisms were identified as instrumental variables for serum 25OHD, Ca and PTH levels, respectively. There was no significant association between genetically predicted serum 25OHD levels and the risk of CAD in patients with diabetes (odds ratio (OR) = 1.04, 95% confidence interval (CI): 0.58 - 1.87, P = 0.888). Similarly, genetically predicted serum Ca (OR = 1.83, 95% CI: 0.62 - 5.35, P = 0.273) and PTH levels (OR = 1.27, 95% CI: 0.67 - 2.44, P = 0.464) were not significantly associated with the risk of CAD in patients with diabetes. These findings were robust in sensitivity analyses. CONCLUSIONS/INTERPRETATION: Serum 25OHD, Ca and PTH levels may not be causally associated with the risk of CAD in patients with diabetes.

Analysis of serum levels L-arginine and 25-hydroxyvitamin D as a predictor of survival of severe preeclampsia mothers

Objective: This study aimed to analyze serum levels of L-arginine and 25-hydroxyvitamin D as predictors of survival in severely preeclamptic women. Methods: This study is a retrospective descriptive study using medical record data from June to August 2019 and has received a recommendation for ethical approval with the protocol number UH20070290. The study was conducted in 4 hospitals in Makassar: Dr. General Hospital. Wahidin Sudirohusodo, Hasanuddin University Teaching Hospital, Siti Fatimah Regional Mother and Child Health Hospital, and Sitti Khadijah 1 Mother and Child Hospital. The samples of this study were mothers who gave birth with a diagnosis of normal pregnant women, severe preeclampsia, and severe preeclampsia with complications. Results: Serum l-arginine level did not affect the survival of severe preeclamptic mothers. It was shown at p-value 0.799 > 0.05. Meanwhile, serum levels of 25-hydroxyvitamin D affect the predictors of maternal preeclampsia where the p-value is 0.024 < 0.05. In comparing serum levels of L-arginine and 25-hydroxyvitamin D, there was no significant difference in groups of normal pregnant women, severe preeclampsia, and severe preeclampsia with complications. Conclusion: Serum level of 25-hydroxyvitamin affects the survival of severe preeclamptic mothers. (AU)

25 Hydroxyvitamin D Levels are Negatively and Independently Associated with Fat Mass in a Cohort of Healthy Overweight and Obese Subjects.

BACKGROUND: Obesity is associated with lower serum vitamin D (25(OH)D) levels through several mechanisms. The aim of the study was to examine the possibility of a negative association between fat mass and 25(OH)D levels in a cohort of otherwise healthy overweight and obese subjects, independently of age, sex, blood pressure levels and anthropometric and metabolic parameters. MATERIALS AND METHODS: 147 overweight and obese subjects (106 women and 41 men), aged between 18 and 69 years, were enrolled into the study. All of them did not show any clinically evident metabolic or chronic diseases (i.e. hypertension, diabetes mellitus, renal failure, etc.) and did not use any kind of drug. Serum fasting levels of 25(OH)D, insulin, glucose, uric acid and lipids (triglycerides, total, HDL and LDL cholesterol) were measured. The season in which the blood samples were collected was autumn. Insulin resistance was assessed by using the Homeostasis Model Assessment (HOMA-IR). Body composition parameters (Fat Mass [FM], Fat Free Mass [FFM], body cell mass [BCM], Total Body Water [TBW]) were measured by electrical Bioimpedance Analysis (BIA). Lastly, demographic, anthropometric and clinical parameters (age, Body Mass Index [BMI], Waist Circumference [WC], Systolic (SBP) and Diastolic (DBP) blood pressure) were also assessed. RESULTS: 25(OH)D levels were significantly and negatively correlated with BMI (P <0.001), WC (P <0.01), DBP (P <0.05), insulin (P <0.001), HOMA-IR (P <0.01), triglycerides (P <0.01), and fat mass (P <0.001). A multivariate regression analysis was performed by considering 25(OH)D levels as the dependent variable and sex, waist circumference, fat mass, DBP, triglycerides, and insulin (or HOMAIR) as the independent ones, and 25(OH)D levels maintained a significant and independent relationship only with fat mass (negative) (P <0.01). CONCLUSION: This study clearly shows that 25(OH)D circulating levels are progressively lower with the increase of fat mass, independently of sex, body fat distribution, blood pressure and insulin and metabolic parameters. These data strongly show that adipose tissue accumulation per se is absolutely the main factor responsible factor for lower 25(OH)D levels in obese subjects, possibly through sequestration of fat soluble 25(OH)D in fat mass.

Serum 25-Hydroxyvitamin D Levels and the Risk of Dysplasia and Esophageal Adenocarcinoma in Patients with Barrett's Esophagus.

BACKGROUND: To date, there are no studies reporting an association between vitamin D and Barrett's esophagus (BE), the precursor for esophageal adenocarcinoma (EAC). AIMS: Our aim was to study the association between serum 25-hydroxyvitamin D (25(OH)D) levels and prevalence and incidence of dysplasia/EAC in BE. METHODS: Patients from our BE Registry cohort seen between 2000 and 2012 who had serum 25(OH)D levels measured were included. Age, gender, race, BE length, hiatal hernia size, and histological findings were recorded. Patients without high-grade dysplasia (HGD)/EAC at or within 1 year of index biopsy and who had follow-up endoscopies and 25(OH)D levels were studied for incidence of dysplasia/EAC. RESULTS: Among 429 patients with BE, the mean 25(OH)D level was 72 ± 31.2 nmol/L. Hundred and one (23.6 %) patients had deficiency (<50 nmol/L), 149 (34.7 %) had insufficiency (50-74.9 nmol/L), and 179 (41.7 %) had normal levels of 25(OH)D. There was no association between serum 25(OH)D levels and dysplasia (p = 0.90). In the incidence cohort of 246 patients with median follow-up of 46 months, there were 34 cases of low-grade dysplasia, 12 of HGD, and 5 of EAC. Change in 25(OH)D levels did not impact progression to dysplasia/EAC (every 5 nmol/L increase from baseline, hazard ratio 0.98; p = 0.62). CONCLUSIONS: Serum 25(OH)D levels were low in 58.3 % of our BE cohort. There was no association between 25(OH)D levels and prevalence or incidence of HGD/EAC in patients with BE. Further long-term studies are needed to study the association between vitamin D status and progression of dysplasia in BE.

Circulating levels of vitamin D and colorectal adenoma: A case-control study and a meta-analysis.

AIM: To examine the association between circulating 25-hydroxyvitamin D [25(OH)D] levels and colorectal adenoma in a case-control study and a meta-analysis. METHODS: We conducted a matched case-control study (112 cases and 112 matched controls) and combined 15 studies, including our study, in a meta-analysis. The study-specific odds ratios (ORs) and 95% confidence intervals (CIs) were pooled using a random-effects model. In total, 5454 colorectal adenomas and 6656 controls were included in the meta-analysis. RESULTS: In a meta-analysis including 14 previous studies and our study, we observed a significant inverse association between circulating 25(OH)D levels and colorectal adenoma (OR = 0.68; 95%CI: 0.54-0.82) when comparing the highest category with the lowest category. Stratification by adenoma location (proximal or distal adenoma) showed similar estimates. When we stratified by study region, the ORs (95%CIs) were 0.70 (0.52-0.88) in the US and 0.66 (0.34-0.97) in Asia. CONCLUSION: These data suggest an inverse association between circulating 25(OH)D levels and colorectal adenoma in both Western and Asian populations.