Identification of VKORC1 genotype leading to resistance to tecarfarin

Matagrin, Benjamin; Montagut-Romans, Adrien; Damin, Marlene; Lemaire, Marc; Popowycz, Florence; Benoît, Etienne; Lattard, Virginie

doi:10.1002/jcph.332

Cited by 3 publications

(3 citation statements)

References 24 publications

(65 reference statements)

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“…Although the first detailed enzymatic studies of VKOR activity in liver microsomes prepared from mice and rats commenced in 1984 [ 58 , 59 , 60 ], more recent studies, since 2011, characterizing the enzymatics of recombinantly produced human and rat VKORC1 and VKORC1L1 are just now gaining momentum among several active, independent research groups [ 31 , 52 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 ]. In order to form a comprehensive picture of our current understanding of VKOR enzymatics, we have summarized the basic results of these studies ( Table 1 ).…”

Section: Common Aspects Of Vkorc1 and Vkorc1l1 Structure And Functmentioning

confidence: 99%

“…To achieve this, the enzymes function by a kinetic mechanism that alternates between two states where the active site CXXC motif cysteines are either oxidized (in the form of a disulfide bridge between them) or reduced [ 58 , 63 , 65 , 69 ]. Two different enzyme kinetic models have thus far been applied to VKOR studies—the “ping-pong” model takes enzymatic conversion of both substrates into account [ 58 , 63 , 65 , 68 ], while a simpler Michaelis–Menton single substrate kinetic model is based on enzymatic conversion of only the K>O substrate [ 31 , 52 , 59 , 60 , 61 , 62 , 64 , 66 , 67 ]. For the K>O single substrate model to be valid, the DTT substrate must be at saturating concentration in the VKOR assay a requisite condition for pseudo first-order kinetics [ 70 ].…”

Section: Common Aspects Of Vkorc1 and Vkorc1l1 Structure And Functmentioning

confidence: 99%

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VKORC1 and VKORC1L1: Why do Vertebrates Have Two Vitamin K 2,3-Epoxide Reductases?

Oldenburg¹,

Watzka²,

Bevans³

2015

Nutrients

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Among all cellular life on earth, with the exception of yeasts, fungi, and some prokaryotes, VKOR family homologs are ubiquitously encoded in nuclear genomes, suggesting ancient and important biological roles for these enzymes. Despite single gene and whole genome duplications on the largest evolutionary timescales, and the fact that most gene duplications eventually result in loss of one copy, it is surprising that all jawed vertebrates (gnathostomes) have retained two paralogous VKOR genes. Both VKOR paralogs function as entry points for nutritionally acquired and recycled K vitamers in the vitamin K cycle. Here we present phylogenetic evidence that the human paralogs likely arose earlier than gnathostomes, possibly in the ancestor of crown chordates. We ask why gnathostomes have maintained these paralogs throughout evolution and present a current summary of what we know. In particular, we look to published studies about tissue- and developmental stage-specific expression, enzymatic function, phylogeny, biological roles and associated pathways that together suggest subfunctionalization as a major influence in evolutionary fixation of both paralogs. Additionally, we investigate on what evolutionary timescale the paralogs arose and under what circumstances in order to gain insight into the biological raison d’être for both VKOR paralogs in gnathostomes.

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Section: Common Aspects Of Vkorc1 and Vkorc1l1 Structure And Functmentioning

confidence: 99%

Section: Common Aspects Of Vkorc1 and Vkorc1l1 Structure And Functmentioning

confidence: 99%

VKORC1 and VKORC1L1: Why do Vertebrates Have Two Vitamin K 2,3-Epoxide Reductases?

Oldenburg¹,

Watzka²,

Bevans³

2015

Nutrients

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“…The heterogeneity of the studies was examined using the Q-test and the I 2 test [12, 13]. If the between-study heterogeneity was significant ( P < 0.05 for the Q-test and I 2 > 50%), we used a random-effects model (DerSimonian-Laird method) [14]; otherwise, the fixed-effects model (Mantel-Haenszel method) was used [15]. The sensitivity was assessed by the omission of individual studies to determine the stability of the results in this meta-analysis.…”

Section: Methodsmentioning

confidence: 99%

ARLTS1 polymorphism is associated with an increased risk of familial cancer: evidence from a meta-analysis

Jiang

Zhao

Cheng

et al. 2017

Hered Cancer Clin Pract

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Adenosine diphosphate (ADP)-ribosylation factor-like tumour suppressor gene 1(ARLTS1) might be associated with an increased risk of several types of familial cancers. However, previous studies have shown that cancer susceptibility is not completely consistent with ARLTS1 polymorphisms, and the precise mechanism remains unknown. Therefore, we conducted a meta-analysis of case-control studies by searching the PubMed, Embase, OVID, Science Direct and Chinese National Knowledge Infrastructure (CNKI) databases. In total, 12 studies met the inclusion criteria and were included in this meta-analysis. Statistical analyses were performed using STATA 11.0 software. Overall, the Cys148Arg T > C variant significantly increased cancer risk (CC vs. TT: OR = 1.27, 95% CI = 1.15–1.41, P < 0.05). The stratification indicated that the Cys148Arg variant is significantly associated with sporadic cancer (CC vs. TT: OR = 1.36, 95% CI = 1.18–1.55) and familial cancer (CC vs. TT: OR = 1.26, 95% CI = 1.12–1.43). Trp149Stop, Pro131Leu, Ser99Ser and Leu132Leu were not correlated with cancer susceptibility. Based on these results, we demonstrated that the ARLTS1 Cys148Arg polymorphism is associated with an increased risk of sporadic cancer and familial cancer, and there were no associations between the other four SNPs (i.e., Trp149Stop, Pro131Leu, Ser99Ser and Leu132Leu) and cancer risk.

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Enantioselective rhodium-catalyzed hydroacylation to access the four stereoisomers of anti-rodent difenacoum

Jacolot

Moebs‐Sanchez

Popowycz

2017

Tetrahedron Letters

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Identification of VKORC1 genotype leading to resistance to tecarfarin

Cited by 3 publications

References 24 publications

VKORC1 and VKORC1L1: Why do Vertebrates Have Two Vitamin K 2,3-Epoxide Reductases?

VKORC1 and VKORC1L1: Why do Vertebrates Have Two Vitamin K 2,3-Epoxide Reductases?

ARLTS1 polymorphism is associated with an increased risk of familial cancer: evidence from a meta-analysis

Enantioselective rhodium-catalyzed hydroacylation to access the four stereoisomers of anti-rodent difenacoum

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