Identification of genetic variants in the human thromboxane synthase gene (CYP5A1)

Chevalier, Dany; Lo-Guidice, Jean-Marc; Sergent, Elodie; Allorge, Delphine; H, Debuysère; Ferrari, Nicolas; Libersa, Christian; Lhermitte, Michel; Broly, Franck

doi:10.1016/s1383-5726(00)00004-2

Cited by 19 publications

(14 citation statements)

References 25 publications

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“…Open boxes Exons, hatching unsequenced regions of repetitive elements, ATG initiation codon, TGA, TAG stop codons Ariyoshi et al (2001) c SNP previously reported by Zhang et al (2002) d SNP previously reported by Lang et al (2001) e SNPs previously reported by Fairbrother et al (1998) f SNP previously reported by Baek et al (1996) g SNP previously reported by Chevalier et al (2001) Gene and variation no. …”

Section: Introductionmentioning

confidence: 97%

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Catalog of 680 variations among eight cytochrome P450 (CYP) genes, nine esterase genes, and two other genes in the Japanese population

et al. 2003

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We screened DNAs from 48 Japanese individuals for single-nucleotide polymorphisms (SNPs) in eight cytochrome P450 (CYP) genes, nine esterase genes, and two other genes by directly sequencing the relevant genomic regions in their entirety except for repetitive elements. This approach identified 607 SNPs and 73 insertion/deletion polymorphisms among the 19 genes examined. Of the 607 SNPs, 284 were identified in CYP genes, 302 in esterase genes, and 21 in the other two genes (GGT1, and TGM1); overall, 37 SNPs were located in 5' flanking regions, 496 in introns, 55 in exons, and 19 in 3' flanking regions. These variants should contribute to studies designed to investigate possible correlations between genotypes and phenotypes of disease susceptibility or responsiveness to drug therapy.Keywords Single-nucleotide polymorphism (SNP) AE Cytochrome P450 (CYP) AE Esterase AE GGT1 AE TGM1

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Section: Introductionmentioning

confidence: 97%

“…TBXAS1 plays an important role in hemostasis and in cardiovascular diseases (FitzGerald et al 1990). Although eleven polymorphisms have been identified in the promoter region, coding sequences, or 3'-untranslated region (3'UTR) of the TBXAS1 gene, the biological effects of these variants are currently unknown (Chevalier et al 2001).…”

Section: Introductionmentioning

confidence: 99%

Catalog of 680 variations among eight cytochrome P450 (CYP) genes, nine esterase genes, and two other genes in the Japanese population

et al. 2003

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“…It consists of 13 exons and spans 193 kb (Tazawa et al 1996). Several polymorphisms have been detected in this gene (Baek et al 1996;Chevalier et al 2001) and a promoter polymorphism has been associated with myocardial infarction in a Japanese population (Tsujita et al 2000).…”

Section: Introductionmentioning

confidence: 99%

Thromboxane synthase (TBXAS1) polymorphisms in African-American and Caucasian populations: evidence for selective pressure

Ulrich

Carlson²,

Sibert

et al. 2005

Hum. Mutat.

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Thromboxane synthase (TBXAS1), a cytochrome P450 enzyme, converts prostaglandin H2 into thromboxane A2, a potent vasoconstrictor and inducer of platelet aggregation. Thromboxane A2 has been implicated in modulating cell cytotoxicity and in tumor growth and metastasis. Twelve coding-region variants were identified in the human TBXAS1 gene in 48 African-American and 46 Caucasian individuals, of which eight were amino-acid substitutions. The latter were confirmed in an independent Caucasian population (n=94 unrelated individuals). We performed an evolutionary analysis of patterns of nucleotide diversity and identified patterns of amino acid replacement in human-mouse comparisons consistent with purifying selection on an inter-species time scale using the McDonald-Kreitman test. We also observed patterns of nucleotide diversity within humans consistent with purifying selection acting on existing polymorphism using Tajima's D within coding regions. These evolutionary tests suggest that some of the rare coding variations observed in the human population are deleterious. We used two sequence-homology-based software programs and molecular modeling to predict the potential impact of these polymorphisms on TBXAS1 function. The c.772C>T (p.Lys258Glu), c.1249C>G (p.Gln417Glu), and c.1348G>A (p.Glu450Lys) substitutions are predicted as most likely to alter protein function; another, c.1352C>A (p.Thr451Asn), may also affect function. Given the evolutionary evidence, these variants may be functional and therefore of relevance for disease endpoints related to inflammation and angiogenesis, as well as for the pharmacogenetics of non-steroidal anti-inflammatory drugs.

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“…Cependant, l'origine moléculaire de ce déficit n'a pas été mise en évidence. Récemment, de nouveaux variants génétiques de la thromboxane synthase ont été identifiés par notre équipe (13 …”

Section: Thromboxane B2 6-keto-pgfla-d4 Lc-esi-ms Human Thromboxanunclassified

Quantification du thromboxane B2 par CLHP-ESI-SM • Application à des microsomes de levure exprimant la thromboxane synthase humaine

Chevalier¹,

Klinzig

Humbert

et al. 2004

Ann Toxicol Anal

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Identification of genetic variants in the human thromboxane synthase gene (CYP5A1)

Cited by 19 publications

References 25 publications

Catalog of 680 variations among eight cytochrome P450 (CYP) genes, nine esterase genes, and two other genes in the Japanese population

Catalog of 680 variations among eight cytochrome P450 (CYP) genes, nine esterase genes, and two other genes in the Japanese population

Thromboxane synthase (TBXAS1) polymorphisms in African-American and Caucasian populations: evidence for selective pressure

Quantification du thromboxane B2 par CLHP-ESI-SM • Application à des microsomes de levure exprimant la thromboxane synthase humaine

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