Association of a novel single nucleotide polymorphism of the prostacyclin synthase gene with myocardial infarction

Nakayama, Tomohiro; Soma, Masayoshi; Saito, Satoshi; Honye, Junko; Yajima, Junji; Rahmutula, Dolkun; Kaneko, Yukie; Sato, Mitsugu; Uwabo, Jiro; Aoi, Noriko; Kosuge, Kotoko; Kunimoto, Masako; Kanmatsuse, Katsuo; Kokubun, Shinichiro

doi:10.1067/mhj.2002.122171

Cited by 48 publications

(33 citation statements)

References 20 publications

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“…SNP2 was not detected in its minor form, whereas SNP1 T22!G was found with the frequency of 84% to 16%, respectively. Previously reported PGIS promoter studies of the VNTR have not reported frequencies for these SNPs (15,17,18,24). Our pooled genomic DNA study revealed that M1 C!T, the SNP occurring within the VNTR repeat itself, have a frequency of 61% and 39% (Table 2).…”

Section: Resultsmentioning

confidence: 84%

Genetic and Epigenetic Regulation of the Human Prostacyclin Synthase Promoter in Lung Cancer Cell Lines

Stearman

Grady

Nana‐Sinkam

et al. 2007

Molecular Cancer Research

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The importance of the arachidonic acid pathway has been established in colon and lung cancers, as well as in inflammatory diseases. In these diseases, prostacyclin I 2 (PGI2) and prostaglandin E 2 (PGE2) are thought to have antagonistic activities, with PGI2 exerting anti-inflammatory and antiproliferative activities, whereas PGE2 is proinflammatory and antiapoptotic. In human lung cancer, prostacyclin synthase (PGIS) and PGI2 are down-regulated, whereas PGE2 synthase (PGES) and PGE2 are up-regulated. Murine carcinogenesis models of human lung cancer reciprocate the relationship between PGIS and PGES expression. PGIS-overexpressing transgenic mice are protected from carcinogen-and tobacco smoke -induced lung tumor formation, suggesting that PGI2 may play a role in chemoprevention. We investigated several potential mechanisms for the down-regulation of PGIS in human lung cancer. Using transcription reporter assays, we show that single nucleotide polymorphisms in the PGIS promoter can affect transcriptional activity. In addition, PGIS expression in several human lung cancer cell lines is silenced by CpG methylation, and we have mapped these sites across the variable number of tandem repeats (VNTR) sequence in the promoter, as well as CpGs within exon 1 and the first intron. Finally, using fluorescence in situ hybridization, we show that human lung cancer cell lines and lung cancer tissues do not have a loss of the PGIS genomic region but multiple copies. These results show that an individual's PGIS promoter haplotype can play an important role in the predisposition for lung cancer and CpG methylation provides an epigenetic mechanism for the down-regulated PGIS expression. (Mol Cancer Res 2007;5(3):295 -308)

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Section: Resultsmentioning

confidence: 84%

Genetic and Epigenetic Regulation of the Human Prostacyclin Synthase Promoter in Lung Cancer Cell Lines

Stearman

Grady

Nana‐Sinkam

et al. 2007

Molecular Cancer Research

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“…Several studies have examined the contribution of PGIS to specific physiological processes, including formation of corpora lutea (64) and regulation of ductus arteriosus patency by inhibition of smooth muscle cell growth (23). Also, disturbances in PGIS have been implicated in different pathomechanisms such as arterial restenosis (92) and myocardial infarction (85). Cotransfection of the PGIS gene with vascular endothelial growth factor in a mouse hindlimb ischemia model was effective in improving therapeutic angiogenesis (58), and gene transfer of PGIS was beneficial in the attenuation of pulmonary hypertension in rats (119).…”

Section: Pgi2 Synthesis and Biologymentioning

confidence: 99%

Prostacyclin signaling in the kidney: implications for health and disease

Nasrallah

Hébert

2005

American Journal of Physiology-Renal Physiology

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The balance between vasodilator and vasoconstrictor pathways is key to the maintenance of homeostasis and the outcome of disease. In the kidney, prostaglandins (PGs) uphold this balance and regulate renal function: hemodynamics, renin secretion, growth responses, tubular transport processes, and cell fate. With the advent of cyclooxygenase (COX)-2-selective inhibitors, targeted deletions in mice (COX knockouts, PG receptor knockouts), and the discovery of intracrine signaling options for PGs (peroxisome proliferator-activated receptors and perinuclear PGE(2) receptors: EP(1,3,4)), many advances have been made in the study of arachidonic acid metabolites. Although prostacyclin (PGI(2)) is a major product of the COX pathway, there is very little emphasis on its importance to the kidney. This review will discuss PGI(2) biology and its relevance to different aspects of renal disease (growth, fibrosis, apoptosis), highlighting the most significant research from the past decade of PGI(2) literature, what we have learned from other organ systems, while stressing the significance of cross talk between various PGI(2) signaling pathways and its implications for renal health and disease.

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“…A positive family history was defined as hypertension diagnosed in parents, grandparents, or siblings. All subjects gave informed consent, and the study was approved by the ethics committee of Nihon University [12].…”

Section: Subjectsmentioning

confidence: 99%

Two medium-chain acyl-coenzyme A synthetase genes, SAH and MACS1, are associated with plasma high-density lipoprotein cholesterol levels, but they are not associated with essential hypertension

Haketa

Soma²,

Nakayama³

et al. 2004

Journal of Hypertension

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Association of a novel single nucleotide polymorphism of the prostacyclin synthase gene with myocardial infarction

Cited by 48 publications

References 20 publications

Genetic and Epigenetic Regulation of the Human Prostacyclin Synthase Promoter in Lung Cancer Cell Lines

Genetic and Epigenetic Regulation of the Human Prostacyclin Synthase Promoter in Lung Cancer Cell Lines

Prostacyclin signaling in the kidney: implications for health and disease

Two medium-chain acyl-coenzyme A synthetase genes, SAH and MACS1, are associated with plasma high-density lipoprotein cholesterol levels, but they are not associated with essential hypertension

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