ArticleArthritis research & therapy2006
NOS2 polymorphisms associated with the susceptibility to pulmonary arterial hypertension with systemic sclerosis: contribution to the transcriptional activity.
Article in Arthritis research & therapy, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- A systematic review of genetic mutations in pulmonary arterial hypertension.BMC medical genetics · 2017Pooled it
- Molecular Pathogenesis of Connective Tissue Disease-Associated Pulmonary Arterial Hypertension: A Narrative Review.Biomolecules · 2025Review
- Updates on genetics in systemic sclerosis.Inflammation and regeneration · 2021Review
- Polymorphisms in oxidative pathway related genes and susceptibility to inflammatory bowel disease.World journal of gastroenterology · 2017Article
- Inducible nitric oxide synthase gene polymorphisms are associated with a risk of nephritis in Henoch-Schönlein purpura children.European journal of pediatrics · 2017Article
- Association evidence of CCTTT repeat polymorphism in the iNOS promoter and the risk of atrial fibrillation in Taiwanese.Scientific reports · 2017Article
- Exhaled Nitric Oxide in Systemic Sclerosis Lung Disease.Canadian respiratory journal · 2017Article
- Outcome after BCG treatment for urinary bladder cancer may be influenced by polymorphisms in the NOS2 and NOS3 genes.Redox biology · 2015Article
- Pathogenesis of Systemic Sclerosis.Frontiers in immunology · 2015Review
- The (CCTTT)n microsatellite polymorphism in the NOS2 gene may influence lung cancer risk and long-term survival, especially in non-smokers.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Article
- Unraveling the genetic component of systemic sclerosis.Human genetics · 2012Review
- Genetic markers of cardiovascular disease in rheumatoid arthritis.Mediators of inflammation · 2012Review
- Pulmonary vascular disease related to hemodynamic stress in the pulmonary circulation.Comprehensive Physiology · 2011Review
- Pulmonary Arterial Hypertension-A Deadly Complication of Systemic Sclerosis.Journal of clinical rheumatology & musculoskeletal medicine · 2010Article
- Two polypyrimidine tracts in the nitric oxide synthase 2 gene: similar regulatory sequences with different properties.Molecular biology reports · 2010Article
- Genetics of systemic sclerosis-associated pulmonary arterial hypertension: recent progress and current concepts.Current rheumatology reports · 2009Review
- [Scleroderma in childhood and adolescence. New aspects on classification, etiology and therapy].Zeitschrift fur Rheumatologie · 2008Review
- Pathogenic mechanisms of pulmonary arterial hypertension.Journal of molecular and cellular cardiology · 2008Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Systemic sclerosis (SSc) is a connective tissue disease characterized by tissue fibrosis. One of several complications of SSc, pulmonary arterial hypertension (PAH) can be refractory to treatment, both novel and established. In the present study we investigated the ratio of circulating nitric oxide to endothelin-1 in patients with both SSc and PAH, and determined whether polymorphisms in NOS2 (the nitric oxide synthase 2 gene) are associated with susceptibility to PAH. Endothelin-1 in plasma and nitric oxide metabolites (nitrate and nitrite) in serum were measured. The nitric oxide/endothelin-1 ratio was significantly lower in patients with both SSc and PAH than in patients with SSc only or in healthy control individuals. We confirmed the presence of two single nucleotide polymorphisms at positions -1,026 and -277 and a pentanucleotide repeat (CCTTT) at -2.5 kilobases. There were significant differences in single nucleotide polymorphisms between patients with SSc who had PAH and those who did not, and between patients with both SSc and PAH and healthy control individuals. The CCTTT repeat was significantly shorter in patients with both SSc and PAH than in patients with SSc only or in healthy control individuals. Transcriptional activity were analyzed using the luciferase reporter assay. The transcriptional activity of NOS2 was much greater in fibroblasts transfected by a vector with a long allele of the CCTTT repeat than in those transfected by a vector with a short allele. Polymorphisms in the NOS2 gene are associated with transcriptional activity of the NOS2 gene and with susceptibility to SSc-related PAH.
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Registered trials
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