Splicing mutation of the prostacyclin synthase gene in a family associated with hypertension. Export

@article{nakayama02, abstract = {Prostacyclin inhibits platelet aggregation, smooth muscle cell proliferation, and vasoconstriction. The prostacyclin synthase (PGIS) gene is a candidate gene for cardiovascular disease. The purpose of this study was to locate possible mutations in the PGIS gene related to hypertension and cerebral infarction. Using the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) method, we discovered a T to C transition at the +2 position of the splicing donor site of intron 9 in patients with essential hypertension (EH). In vitro expression analysis of an allelic minigene consisting of exons 8-10 revealed that the nucleotide transition causes skipping of exon 9. This in turn alters the translational reading frame of exon 10 and introduces a premature stop codon (TGA). A three-dimensional model shows that the splice site mutation produces a truncated protein with a deletion in the heme-binding region. This splice site mutation was found in only one subject in 200 EH patients and 200 healthy controls. Analysis of the patient's family members revealed the mutation in two of the three siblings. The urinary excretion of prostacyclin metabolites in subjects with the mutation was significantly decreased. All subjects displaying the splice site mutation in the PGIS gene were hypertensive. In this study, we report a novel splicing mutation in the PGIS gene, which is associated with hypertension in a family. It is thought that this mechanism may involve in the pathophysiology of their hypertension.}, author = {Nakayama, Tomohiro and Soma, Masayoshi and Watanabe, Yoshiyasu and Hasimu, Buaijiaer and Sato, Mikano and Aoi, Noriko and Kosuge, Kotoko and Kanmatsuse, Katsuo and Kokubun, Shinichiro and Marrow, Jason D. and Oates, John A.}, citeulike-article-id = {1437462}, journal = {Biochem Biophys Res Commun}, keywords = {12372404, alleles, biosynthesis, combinedbib, conformational, cytochrome, data, enzyme, exons, family, female, genetic, genotype, govt, health, humans, hypertension, intramolecular, introns, male, models, molecular, mutation, non-us, oxidoreductases, p-450, pedigree, phs, polymorphism, protein, research, rna, sequence, single-stranded, splicing, support, system, us}, month = {Oct}, number = {5}, pages = {1135--9}, posted-at = {2007-07-05 14:55:21}, priority = {2}, title = {Splicing mutation of the prostacyclin synthase gene in a family associated with hypertension.}, volume = {297}, year = {2002} }

TY - JOUR ID - nakayama02 L3 - citeulike-article-id:1437462 N2 - Prostacyclin inhibits platelet aggregation, smooth muscle cell proliferation, and vasoconstriction. The prostacyclin synthase (PGIS) gene is a candidate gene for cardiovascular disease. The purpose of this study was to locate possible mutations in the PGIS gene related to hypertension and cerebral infarction. Using the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) method, we discovered a T to C transition at the +2 position of the splicing donor site of intron 9 in patients with essential hypertension (EH). In vitro expression analysis of an allelic minigene consisting of exons 8-10 revealed that the nucleotide transition causes skipping of exon 9. This in turn alters the translational reading frame of exon 10 and introduces a premature stop codon (TGA). A three-dimensional model shows that the splice site mutation produces a truncated protein with a deletion in the heme-binding region. This splice site mutation was found in only one subject in 200 EH patients and 200 healthy controls. Analysis of the patient's family members revealed the mutation in two of the three siblings. The urinary excretion of prostacyclin metabolites in subjects with the mutation was significantly decreased. All subjects displaying the splice site mutation in the PGIS gene were hypertensive. In this study, we report a novel splicing mutation in the PGIS gene, which is associated with hypertension in a family. It is thought that this mechanism may involve in the pathophysiology of their hypertension. IS - 5 JF - Biochem Biophys Res Commun EP - 9 TI - Splicing mutation of the prostacyclin synthase gene in a family associated with hypertension. VL - 297 SP - 1135 KW - 12372404 KW - alleles KW - biosynthesis KW - combinedbib KW - conformational KW - cytochrome KW - data KW - enzyme KW - exons KW - family KW - female KW - genetic KW - genotype KW - govt KW - health KW - humans KW - hypertension KW - intramolecular KW - introns KW - male KW - models KW - molecular KW - mutation KW - non-us KW - oxidoreductases KW - p-450 KW - pedigree KW - phs KW - polymorphism KW - protein KW - research KW - rna KW - sequence KW - single-stranded KW - splicing KW - support KW - system KW - us AU - Nakayama, Tomohiro AU - Soma, Masayoshi AU - Watanabe, Yoshiyasu AU - Hasimu, Buaijiaer AU - Sato, Mikano AU - Aoi, Noriko AU - Kosuge, Kotoko AU - Kanmatsuse, Katsuo AU - Kokubun, Shinichiro AU - Marrow, Jason AU - Oates, John PY - 2002/Oct// ER -