Polymorphisms Related to the Serum 25-Hydroxyvitamin D Level and Risk of Myocardial Infarction, Diabetes, Cancer and Mortality. The Tromsø Study

Jorde, Rolf; Schirmer, Henrik; Wilsgaard, Tom; Joakimsen, Ragnar Martin; Mathiesen, Ellisiv B.; Njølstad, Inger; Løchen, Maja‐Lisa; Figenschau, Yngve; Berg, Jens Petter; Svartberg, Johan; Grimnes, Guri

doi:10.1371/journal.pone.0037295

Cited by 100 publications

(101 citation statements)

References 43 publications

(79 reference statements)

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“…Since the discovery of the VDR gene, common single nucleotide polymorphisms (SNPs) have been described in the gene encoding VDR [14]. Three common VDR-SNPs (FokI, ApaI and BsmI) have been extensively investigated and associated with several diseases [9,[15][16][17][18][19][20]. However, although there is evidence for a genetic contribution to hypertensive disorders of pregnancy [21][22][23], no previous study has examined whether VDR polymorphisms affect the susceptibility to such disorders of pregnancy.…”

Section: Introductionmentioning

confidence: 99%

Vitamin D receptor polymorphisms in hypertensive disorders of pregnancy

et al. 2012

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Hypertension is the most common medical disorder in pregnancy, and a leading cause of maternal and neonatal morbidity and mortality. Vitamin D endocrine system has important influence on immune modulation and endothelial function, which play a role in preeclampsia (PE) and gestational hypertension (GH). Vitamin D receptor (VDR) is present in a large variety of cell types, including placental cells. We examined whether there is an association between VDR polymorphisms (FokI, ApaI and BsmI) with PE or with GH. Restriction fragment length polymorphism techniques were used to genotype 529 pregnant (154 with GH, 162 with PE, and 213 healthy pregnant-HP). VDR haplotype frequencies were inferred using the PHASE 2.1 program. We found similar genotype distributions for the three VDR polymorphisms in both PE and GH groups compared with the HP group (all P [ 0.05). In parallel with these findings, the VDR haplotype frequency distribution was similar in both PE and GH groups compared with the HP group (all P [ 0.05). Our results showing no significant association between VDR polymorphisms or haplotypes with PE or GH suggest that genetic variations in VDR do not predispose to hypertensive disorders of pregnancy.

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Section: Introductionmentioning

confidence: 99%

Vitamin D receptor polymorphisms in hypertensive disorders of pregnancy

et al. 2012

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“…Nonfasting blood samples were analyzed consecutively for serum total cholesterol, triglycerides, and high-density lipoprotein cholesterol (HDL-cholesterol) in all subjects (5), and serum TSH (9) and HbA 1c (17) were determined in subgroups. DNA was prepared from blood clots stored at the national CONOR (Cohort of Norway) bio-bank, located at the HUNT/NTNU biobank in Levanger (18). The SNP rs4704397 was selected due to the reported strong association with serum TSH levels (13)(14)(15).…”

Section: Measurements In 1994mentioning

confidence: 99%

“…The SNP rs4704397 was selected due to the reported strong association with serum TSH levels (13)(14)(15). The genotyping was performed by LGC Genomics (formerly KBioscience, Hoddesdon, United Kingdom) using the KBioscience Competitive Allele-Specific PCR genotyping system (18).…”

Section: Measurements In 1994mentioning

confidence: 99%

“…The selection of subjects for the genetic studies has been described in detail previously (18). In short, the subjects were primarily selected for evaluation of genetic polymorphisms and hard endpoints for which there are several registers in the Tromsø Study.…”

Section: Selection Of Subjects For Genetic Studiesmentioning

confidence: 99%

“…The definitions of incident MI and T2DM have previously been described in detail (18,20,21). Information on cancer incidence and cancer location was retrieved from the Cancer Registry of Norway.…”

Section: Definition Of Endpointsmentioning

confidence: 99%

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The Phosphodiesterase 8B Gene rs4704397 is Associated with Thyroid Function, Risk of Myocardial Infarction, and Body Height: The Tromsø Study

Jorde

Schirmer

Wilsgaard

et al. 2014

Thyroid

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Objective: High serum thyrotropin (TSH) levels predict cardiovascular disease (CVD). Recently several single nucleotide polymorphisms (SNPs) associated with TSH levels have been identified, one of them being the rs4704397 SNP in the phosphodiesterase 8B (PDE8B) gene. If the relation between thyroid function and CVD is causal, one could also expect rs4704397 genotypes to predict CVD and possibly health in general. Methods: DNA was prepared and genotyping performed for rs4704397 in subjects who participated in the fourth survey of the Tromsø Study in 1994-1995 and who were registered with the endpoints myocardial infarction (MI), type 2 diabetes (T2DM), cancer, or death, as well as a randomly selected control group. Similarly, genotyping was performed in subjects who had participated in clinical trials where serum TSH, free T4 (fT4), and free T3 (fT3) were measured. Results: From the Tromsø Study, 8938 subjects without thyroid disease or thyroid medication were successfully genotyped for rs4704397. Among these, 2098 were registered with MI, 1025 with T2DM, 2748 with cancer, and 3592 had died. The minor homozygote genotype (A:A) had a median serum TSH level that was 0.29 mIU/L higher than in the major homozygote genotype (G:G). The A:A genotype had a significantly increased risk of MI as compared to the G:G genotype (1.14 [1.00-1.29], hazard ratio [confidence interval], Cox regression with adjustment for age, sex, and body mass index). No significant associations were seen with the other endpoints or CVD risk factors. Furthermore, subjects with the G:G genotype were significantly taller than subjects with the A:A genotype (mean difference 1.5 cm). In 584 subjects with serum TSH, fT4, and fT3 measurements, the subjects with the A:A genotype had significantly higher serum TSH and nonsignificantly lower serum fT3 (mean difference 0.15 pmol/L) levels than subjects with the G:G genotype. Conclusion: rs4704397 is associated with thyroid function, risk of MI, and body height. However, confirmation in other cohorts is needed before firm conclusions can be drawn.

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Effect of Monthly High-Dose Vitamin D Supplementation on Cardiovascular Disease in the Vitamin D Assessment Study

et al. 2017

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IMPORTANCE Cohort studies have reported increased incidence of cardiovascular disease (CVD) among individuals with low vitamin D status. To date, randomized clinical trials of vitamin D supplementation have not found an effect, possibly because of using too low a dose of vitamin D. OBJECTIVE To examine whether monthly high-dose vitamin D supplementation prevents CVD in the general population. DESIGN, SETTING, AND PARTICIPANTSThe Vitamin D Assessment Study is a randomized, double-blind, placebo-controlled trial that recruited participants mostly from family practices in Auckland, New Zealand, from April 5, 2011, through November 6, 2012, with follow-up until July 2015. Participants were community-resident adults aged 50 to 84 years. Of 47 905 adults invited from family practices and 163 from community groups, 5110 participants were randomized to receive vitamin D 3 (n = 2558) or placebo (n = 2552). Two participants retracted consent, and all others (n = 5108) were included in the primary analysis.INTERVENTIONS Oral vitamin D 3 in an initial dose of 200 000 IU, followed a month later by monthly doses of 100 000 IU, or placebo for a median of 3.3 years (range, 2.5-4.2 years). MAIN OUTCOMES AND MEASURESThe primary outcome was the number of participants with incident CVD and death, including a prespecified subgroup analysis in participants with vitamin D deficiency (baseline deseasonalized 25-hydroxyvitamin D [25(OH)D] levels <20 ng/mL). Secondary outcomes were myocardial infarction, angina, heart failure, hypertension, arrhythmias, arteriosclerosis, stroke, and venous thrombosis. RESULTSOf the 5108 participants included in the analysis, the mean (SD) age was 65.9 (8.3) years, 2969 (58.1%) were male, and 4253 (83.3%) were of European or other ethnicity, with the remainder being Polynesian or South Asian. Mean (SD) baseline deseasonalized 25(OH)D concentration was 26.5 (9.0) ng/mL, with 1270 participants (24.9%) being vitamin D deficient. In a random sample of 438 participants, the mean follow-up 25(OH)D level was greater than 20 ng/mL higher in the vitamin D group than in the placebo group. The primary outcome of CVD occurred in 303 participants (11.8%) in the vitamin D group and 293 participants (11.5%) in the placebo group, yielding an adjusted hazard ratio of 1.02 (95% CI, 0.87-1.20). Similar results were seen for participants with baseline vitamin D deficiency and for secondary outcomes.CONCLUSIONS AND RELEVANCE Monthly high-dose vitamin D supplementation does not prevent CVD. This result does not support the use of monthly vitamin D supplementation for this purpose. The effects of daily or weekly dosing require further 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

Cited by 100 publications

References 43 publications

Vitamin D receptor polymorphisms in hypertensive disorders of pregnancy

Vitamin D receptor polymorphisms in hypertensive disorders of pregnancy

The Phosphodiesterase 8B Gene rs4704397 is Associated with Thyroid Function, Risk of Myocardial Infarction, and Body Height: The Tromsø Study

Effect of Monthly High-Dose Vitamin D Supplementation on Cardiovascular Disease in the Vitamin D Assessment Study

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