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Polymorphisms related to the serum 25-hydroxyvitamin D level and risk of myocardial infarction, diabetes, cancer and mortality. The Tromso Study.

ABSTRACT: Low serum 25(OH)D levels are associated with cardiovascular risk factors, and also predict future myocardial infarction (MI), type 2 diabetes (T2DM), cancer and all-cause mortality. Recently several single nucleotide polymorphisms (SNPs) associated with serum 25-hydroxyvitamin D (25(OH)D) level have been identified. If these relations are causal one would expect a similar association between these SNPs and health.DNA was prepared from subjects who participated in the fourth survey of the Tromsø Study in 1994-1995 and who were registered with the endpoints MI, T2DM, cancer or death as well as a randomly selected control group. The endpoint registers were complete up to 2007-2010. Genotyping was performed for 17 SNPs related to the serum 25(OH)D level.A total of 9528 subjects were selected for genetic analyses which were successfully performed for at least one SNP in 9471 subjects. Among these, 2025 were registered with MI, 1092 with T2DM, 2924 with cancer and 3828 had died. The mean differences in serum 25(OH)D levels between SNP genotypes with the lowest and highest serum 25(OH)D levels varied from 0.1 to 7.8 nmol/L. A genotype score based on weighted risk alleles regarding low serum 25(OH)D levels was established. There was no consistent association between the genotype score or individuals SNPs and MI, T2DM, cancer, mortality or risk factors for disease. However, for rs6013897 genotypes (located at the 24-hydroxylase gene (CYP24A1)) there was a significant association with breast cancer (P<0.05).Our results do not support nor exclude a causal relationship between serum 25(OH)D levels and MI, T2DM, cancer or mortality, and our observation on breast cancer needs confirmation. Further genetic studies are warranted, particularly in populations with vitamin D deficiency.ClinicalTrials.gov NCT01395303.

SUBMITTER: Jorde R

PROVIDER: S-EPMC3359337 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Polymorphisms related to the serum 25-hydroxyvitamin D level and risk of myocardial infarction, diabetes, cancer and mortality. The Tromsø Study.

Jorde Rolf R Schirmer Henrik H Wilsgaard Tom T Joakimsen Ragnar Martin RM Mathiesen Ellisiv Bøgeberg EB Njølstad Inger I Løchen Maja-Lisa ML Figenschau Yngve Y Berg Jens Petter JP Svartberg Johan J Grimnes Guri G

PloS one 20120523 5

<h4>Objective</h4>Low serum 25(OH)D levels are associated with cardiovascular risk factors, and also predict future myocardial infarction (MI), type 2 diabetes (T2DM), cancer and all-cause mortality. Recently several single nucleotide polymorphisms (SNPs) associated with serum 25-hydroxyvitamin D (25(OH)D) level have been identified. If these relations are causal one would expect a similar association between these SNPs and health.<h4>Methods</h4>DNA was prepared from subjects who participated i ...[more]

PMID: 22649517

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Project description:BackgroundVaccination is an important strategy in the prevention of influenza, but immunologic response to vaccination can vary widely. Recent studies have shown an association between serum 25-hydroxyvitamin D (25[OH]D) levels and immune function. The purpose of this study was to determine if serum 25(OH)D level correlates with influenza vaccine immunogenicity in children and adolescents.MethodsWe conducted a prospective cohort study of children age 3 to 15 years of age vaccinated with trivalent influenza vaccine (A/Brisbane/59/2007[H1N1]-like virus, A/Brisbane/10/2007 [H3N2]-like virus and B/Florida/4/2006-like virus) in Hutterite communities in Alberta, Saskatchewan and Manitoba. Serum 25(OH)D levels were measured at baseline and immunogenicity was assessed using hemagluttination inhibition (HAI) titers done at baseline and 3-5 weeks post vaccination. Logistic regression was used to assess the relationship between serum 25(OH)D level as both a continuous and dichotomous variable and seroprotection, seroconversion, fold increase in geometric mean titer (GMT) and post vaccination titer.ResultsA total of 391 children and adolescents were included in the study and 221 (57% had post-vaccination HAI titers. The median serum 25(OH)D level was 61.0 nmol/L (Interquartile range [IQR] 50.0, 71.0). No relationship was found between serum 25(OH)D level and seroprotection (post-vaccination titer ≥ 40 and ≥ 320) or seroconversion (post-vaccination titer ≥ 40 for participants with pre-vaccine titer <10 or four-fold rise in post-vaccination titer for those with a pre-vaccine titer ≥ 10).ConclusionSerum 25(OH)D level was not associated with influenza vaccine immunogenicity in otherwise healthy children and adolescents. Other strategies to enhance influenza vaccine response should continue to be evaluated in this population. The role of serum 25(OH)D level in vaccine responsiveness in other populations, especially those hyporesponsive to influenza vaccination, requires further study.

Project description:ObjectiveWe hypothesized that deficiency in 25-hydroxyvitamin D before hospital admission would be associated with all-cause mortality in the critically ill.DesignMulticenter observational study of patients treated in medical and surgical intensive care units.SettingA total of 209 medical and surgical intensive care beds in two teaching hospitals in Boston, MA.PatientsA total of 2399 patients, age ≥ 18 yrs, in whom 25-hydroxyvitamin D was measured before hospitalization between 1998 and 2009.InterventionsNone.Measurements and main resultsPreadmission 25-hydroxyvitamin D was categorized as deficiency in 25-hydroxyvitamin D (≤ 15 ng/mL), insufficiency (16-29 ng/mL), and sufficiency (≥ 30 ng/mL). Logistic regression examined death by days 30, 90, and 365 post-intensive care unit admission, in-hospital mortality, and blood culture positivity. Adjusted odds ratios were estimated by multivariable logistic regression models. Preadmission 25-hydroxyvitamin D deficiency is predictive for short-term and long-term mortality. At 30 days following intensive care unit admission, patients with 25-hydroxyvitamin D deficiency have an odds ratio for mortality of 1.69 (95% confidence interval of 1.28-2.23, p < .0001) relative to patients with 25-hydroxyvitamin D sufficiency. 25-Hydroxyvitamin D deficiency remains a significant predictor of mortality at 30 days following intensive care unit admission following multivariable adjustment (adjusted odds ratio of 1.69, 95% confidence interval of 1.26-2.26, p < .0001). At 30 days following intensive care unit admission, patients with 25-hydroxyvitamin D insufficiency have an odds ratio of 1.32 (95% confidence interval of 1.02-1.72, p = .036) and an adjusted odds ratio of 1.36 (95% confidence interval of 1.03-1.79, p = .029) relative to patients with 25-hydroxyvitamin D sufficiency. Results were similar at 90 and 365 days following intensive care unit admission and for in-hospital mortality. In a subgroup analysis of patients who had blood cultures drawn (n = 1160), 25-hydroxyvitamin D deficiency was associated with increased risk of blood culture positivity. Patients with 25-hydroxyvitamin D insufficiency have an odds ratio for blood culture positivity of 1.64 (95% confidence interval of 1.05-2.55, p = .03) relative to patients with 25-hydroxyvitamin D sufficiency, which remains significant following multivariable adjustment (odds ratio of 1.58, 95% confidence interval of 1.01-2.49, p = .048).ConclusionDeficiency of 25-hydroxyvitamin D before hospital admission is a significant predictor of short- and long-term all-cause patient mortality and blood culture positivity in a critically ill patient population.

Project description:Background and objectivesMolecular evidence suggests that levels of vitamin D are associated with kidney function loss. Still, population-based studies are limited and few have considered the potential confounding effect of baseline kidney function. This study evaluated the association of serum 25-hydroxyvitamin D with change in eGFR, rapid eGFR decline, and incidence of CKD and albuminuria.Design, setting, participants, & measurementsBaseline (2003-2006) and 5.5-year follow-up data from a Swiss adult general population were used to evaluate the association of serum 25-hydroxyvitamin D with change in eGFR, rapid eGFR decline (annual loss >3 ml/min per 1.73 m(2)), and incidence of CKD and albuminuria. Serum 25-hydroxyvitamin D was measured at baseline using liquid chromatography-tandem mass spectrometry. eGFR and albuminuria were collected at baseline and follow-up. Multivariate linear and logistic regression models were used considering potential confounding factors.ResultsAmong the 4280 people included in the analysis, the mean±SD annual eGFR change was -0.57±1.78 ml/min per 1.73 m(2), and 287 (6.7%) participants presented rapid eGFR decline. Before adjustment for baseline eGFR, baseline 25-hydroxyvitamin D level was associated with both mean annual eGFR change and risk of rapid eGFR decline, independently of baseline albuminuria. Once adjusted for baseline eGFR, associations were no longer significant. For every 10 ng/ml higher baseline 25-hydroxyvitamin D, the adjusted mean annual eGFR change was -0.005 ml/min per 1.73 m(2) (95% confidence interval, -0.063 to 0.053; P=0.87) and the risk of rapid eGFR decline was null (odds ratio, 0.93; 95% confidence interval, 0.79 to 1.08; P=0.33). Baseline 25-hydroxyvitamin D level was not associated with incidence of CKD or albuminuria.ConclusionsThe association of 25-hydroxyvitamin D with eGFR decline is confounded by baseline eGFR. Sufficient 25-hydroxyvitamin D levels do not seem to protect from eGFR decline independently from baseline eGFR.

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Polymorphisms related to the serum 25-hydroxyvitamin D level and risk of myocardial infarction, diabetes, cancer and mortality. The Tromso Study.

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Polymorphisms related to the serum 25-hydroxyvitamin D level and risk of myocardial infarction, diabetes, cancer and mortality. The Tromsø Study.

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