Genetic and non-genetic correlates of vitamins K and D

Shea, M. Kyla; Benjamin, Emelia J.; Dupuis, Josée; Massaro, Joseph M.; Jacques, Paul F.; D’Agostino, Ralph B.; Ordovas, José M.; O’Donnell, Christopher J.; Dawson‐Hughes, Bess; Vasan, Ramachandran S.; Booth, Sarah L.

doi:10.1038/sj.ejcn.1602959

Cited by 191 publications

(161 citation statements)

References 38 publications

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“…Whereas no significant heritability was reported in 2 biomarkers of vitamin K status in a crosssectional study of almost 2000 subjects, 33 the minor allele G of the identical SNP was associated with higher concentrations 22 Taken together, at the present time, there are insufficient data to support the contention that factors that influence VKORC1 activity potentially modify arterial disease via its chronic impact on peripheral vitamin K status.…”

Section: Discussioncontrasting

confidence: 40%

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Sequence Variation in Vitamin K Epoxide Reductase Gene Is Associated With Survival and Progressive Coronary Calcification in Chronic Kidney Disease

Holden

Booth

Tuttle

et al. 2014

ATVB

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Objective-Sequence variations in the gene(s) encoding vitamin K epoxide reductase complex subunit 1 (VKORC1), the enzyme target of warfarin, have been associated with increased cardiovascular disease in the general population. Coronary artery calcification (CAC) is a prevalent form of cardiovascular disease in chronic kidney disease. We tested the hypothesis that the VKORC1 rs8050894 CC genotype would be associated with mortality and progression of CAC ≤4 years. Approach and Results-This study is an observational, prospective study of 167 individuals with stages 3 to 5 chronic kidney disease. Survival ≤4 years was assessed in all participants, and CAC progression was measured in a subset of 86 patients. Participants with the CG/GG genotype of VKORC1 had higher baseline CAC scores (median score, 112 versus 299; P=0.036). Of those 86 patients who had a 4-year CAC score, those with the CG/GG genotype had an increased risk of progressive CAC (adjusted for age, diabetes mellitus, estimated glomerular filtration rate, and hypertension) compared with those with the CC genotype. Four-year mortality risk was 4 times higher for individuals with the CG/GG genotypes compared with individuals with the CC genotype (odds ratio, 3.8; 95% confidence interval, 1.2-12.5; P=0.02), adjusted for age, sex, diabetes mellitus, estimated glomerular filtration rate, baseline CAC, and hypertension. Conclusions-Patients with the CG/GG genotype of VKORC1 had a higher risk of CAC progression and a poorer survival.These data provide new perspectives on the potential extrahepatic role of VKORC1 in individuals with chronic kidney disease. These data suggest tissue-specific VKOR activity. Sequencing efforts by Rieder et al 10 have yielded 5 common haplotypes of VKORC1 that can be grouped into 2 evolutionarily distant groups called A and B. The A haplotype group is associated with attenuated expression of VKORC1 mRNA in the liver and, as a consequence, lower warfarin requirements.10 Conversely, the B haplotype group is associated with higher expression of VKORC1 mRNA in the liver and higher warfarin requirements. The focus of this study is the singlenucleotide polymorphism (SNP) rs8050894, which has been demonstrated to be in high linkage equilibrium and enables the distinction between these 2 groups. 21 To date, no study has examined the impact of sequence variations of VKORC1 in a CKD population.In this prospective cohort study, performed in a sample of individuals with CKD, we investigated the impact of genetic variations in VKORC1 on survival ≤4 years in a cohort of 167 predialysis stage 3 to 5 CKD patients. In a subset of 86 patients who had follow-up coronary artery calcification (CAC) quantified 4 years later, we examined the associations of sequence variations of VKORC1 on CAC progression. Our hypothesis was that the CC genotype that is associated with decreased warfarin requirements is a nonmodifiable risk factor for CAC and its progression and mortality in patients with CKD are based on low lifetime activity of the vitamin K cycle. Mate...

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Section: Discussioncontrasting

confidence: 40%

Section: Discussionmentioning

confidence: 99%

Sequence Variation in Vitamin K Epoxide Reductase Gene Is Associated With Survival and Progressive Coronary Calcification in Chronic Kidney Disease

Holden

Booth

Tuttle

et al. 2014

ATVB

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“…Results of twin studies have suggested a heritable component of circulating 25-OH-vitamin D concentrations, with heritability rates ranging from 29% to 77% (12,13,14 ). Genomewide association studies identified 3 common loci of genetic determinants for vitamin D insufficiency: group-specific component (GC, rs2282679), 9 7-dehydrocholesterol reductase (DHCR7, rs12785878), and cytochrome P450 IIR-1 (CYP2R1, rs10741657).…”

Section: -Hydroxy-vitamin D (25-oh-vitamin D)mentioning

confidence: 99%

Vitamin D and Mortality: A Mendelian Randomization Study

et al. 2013

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“…Д ля оптимального течения биохимических процессов плоду и новорожденному необ-ходимо адекватное поступление витаминов [1]. Исследования в условиях Европейского Севера не-многочисленны: выявлены особенности обмена витамина С у новорожденных [2], проведено иссле-дование обеспеченности диады мать-ребенок жи-рорастворимыми витаминами А, Е и водораствори-мыми витаминами В 1 , В 2 [3], отмечены особенности метаболического и микронутриентного статуса но-ворожденных детей [4].…”

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