The –786C/T single‐nucleotide polymorphism in the promoter of the gene for endothelial nitric oxide synthase: Insensitivity to physiologic stimuli as a risk factor for rheumatoid arthritis

Melchers, Inga; Blaschke, Sabine; Hecker, Markus; Cattaruzza, Marco

doi:10.1002/art.22147

Cited by 25 publications

(28 citation statements)

References 35 publications

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“…STAT is associated with endothelial expression, transcription and regulations of cytokines, including interleukin, nitric oxide synthesis, p21 and interferon 11. STAT function has been implicated in the transduction of signals for growth, reproduction, viral defense, and immune regulation 12.…”

Section: Discussionmentioning

confidence: 99%

STAT2*C related genotypes and allele but not TLR4 and CD40 gene polymorphisms are associated with higher susceptibility for asthma

Hsieh¹,

Wan²,

Chang³

et al. 2009

Int. J. Biol. Sci.

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Objective: Asthma is caused by a complex interaction between multiple genes and environmental factors. Herein we aimed to investigate whether signal transducer and activator of transcription (STAT2), toll-like receptors 4 (TLRs4) and CD40-related polymorphisms are associated with asthma susceptibility. Design: Children were divided: (1) asthma (n=117); (2) normal controls (n=60). The polymorphisms of STAT2, TLR4 and CD40 polymorphism were analyzed by PCR-RFLP genotyping. Genotypes, allelic frequencies and association of haplotypes in both groups were compared. Results: STAT2*C related genotypes, but not TLR4 and CD40 polymorphism, are associated with higher susceptibility for asthma. Distributions of STAT2*CC/CG/GG and C/G allele in both groups are: (1) 0/11.1/88.9 % and 5.6/94.4%; (2) 0/1.7/98.3% and 0.8/99.2% (p<0.05). Proportions of TLR4*rs10983755 AA/AG/GG and rs1927914 CC/CT/TT homozygote are: (1) 35.1/8.5/56.4% and 9.4/56.4/34.2%; (2) 35/8.3/56.7% and 16.7/48.3/35% (non-difference). Proportions of CD40*rs1883832 CC/CT/TT, rs3765459 AA/AG/GG, and rs4810485 TT/GT/GG are: (1) 29.9/53/17.1%, 6.8/47.9/45.3 and 18.8/62.4/18.8%; (2) 36.7/41.7/21.6%, 1.6/46.7/ 51.7 and 15/51.7/33.3% (non-difference). Haplotype analyses for TLR4 and CD40 genes revealed their non-association and non-additional effect upon asthma susceptibilities. Conclusion: STAT2*C related genotypes and alleles are associated with asthma susceptibilities and pathogenesis. There were non-association and non-additional effects of TLR4/CD40 gene polymorphisms and haplotypes upon asthma risk.

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Section: Discussionmentioning

confidence: 99%

STAT2*C related genotypes and allele but not TLR4 and CD40 gene polymorphisms are associated with higher susceptibility for asthma

Hsieh¹,

Wan²,

Chang³

et al. 2009

Int. J. Biol. Sci.

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“…Because nitric oxide is essential for cellular signalling, it is involved in many physiological and pathological processes including inflammation (Leiper & Nandi, 2011), protection of liver ischemic damage (Yang et al, 2011), carcinogenesis and rheumatoid arthritis (Melchers et al, 2006). Therefore, inhibition of nitric oxide may suggest the mechanism of saponin against inflammation.…”

Section: Discussionmentioning

confidence: 99%

In vitro anti-inflammatory and free radical scavenging activities of crude saponins extracted from Albuca bracteataJacq. Bulb.

Odeyemi¹,

Afolayan²,

Bradley³

2015

Afr. J. Trad. Compl. Alt. Med.

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Background: Albuca bracteata is a medicinal plant traditionally used in the management of diabetes mellitus in the Eastern Cape of South Africa. The purpose of this study was to evaluate the antioxidant and anti-inflammatory activities of saponins extracted from the bulb of Albuca bracteata and compared with the crude methanolic extract. Methods: In vitro antioxidant activity was determined using free radical scavenging assays such as DPPH, ABTS and NO 2 . The antiinflammatory potential was carried out using inhibition of protein denaturation of egg albumin as a model of anti-inflammatory capacity. Results: Both the crude methanolic extract and saponins showed inhibition of DPPH, ABTS and NO 2 scavenging activity. However, the free radical scavenging activity of isolated saponin compared favourably with Rutin and BHT. The crude methanolic extract showed higher inhibition percentage of protein denaturation compared with the saponins at the concentration investigated. Conclusion: This study indicates that saponin from Albuca bracteata bulb possess potent anti-inflammatory activity and is also a good source of natural antioxidant.

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“…Association of the T-786C SNP with HT has yet not been reported in any population study. Recently, the T-786C SNP was shown to be associated with RA in Chinese [30] and German populations [31,32]. Conflicting results demonstrating no association between the T-786C SNP and RA have been reported in Brazilian [33] and Italian [34] populations.…”

Section: Discussionmentioning

confidence: 99%

Influence of Endothelial Nitric Oxide Synthase Gene Intron-4 27bp Repeat Polymorphism on Its Expression in Autoimmune Diseases

AlFadhli

2013

Disease Markers

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Abstract. The purpose of this study was to analyse the effect of the T-786C polymorphism and intron 4 27 bp variable number tandem repeat(VNTR) eNOS markers for their potential association with Systemic Lupus Erythematosus(SLE), Hashimotos thyroiditis(HT) and Rheumatoid arthritis(RA) as well as to explore their effect on eNOS mRNA expression and nitrate production (NOx). Kuwaitis (n = 383) matched by age, gender and ethnicity were genotyped by fluorescent-labelled-restriction fragment length polymorphism (RFLP) and fragment analysis. Expression of eNOS mRNA was analysed using RT-PCR and sera from subjects were screened for NOx using ELISA. Analysis of the allelic frequency revealed a significant association of the 4b allele with susceptibility to SLE (p = 0.0092, OR = 1.76). The 4bb genotype was found to be associated with SLE (p = 0.0076, OR = 1.97) and HT (p = 0.05, OR = 1.81). Allelic and genotypic distribution did not differ between RA patients and healthy control subjects. The 4bb genotype resulted in reduced expression of eNOS mRNA in SLE, RA and HT, but only the reduction in HT was significant (p = 0.05). The 4ab genotype revealed a significant association with increased eNOS expression in HT (p = 0.03) and RA (p = 0.014) patients, and elevated NOx levels were detected in the autoimmune disease cohorts (p < 0.05) when compared to healthy control subjects. The T-786C SNP failed to show a significant association (p > 0.05) with SLE, HT, and RA patients. This study is the first to reveal a significant association between the 4bb genotype of the 27 bp VNTR and susceptibility to HT. The expression of eNOS is related to the number of 27 bp repeats, with heterozygous 4bb repeats showing a decrease in eNOS expression. eNOS -endothelial nitric oxide synthase.

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The ^–786C/T single‐nucleotide polymorphism in the promoter of the gene for endothelial nitric oxide synthase: Insensitivity to physiologic stimuli as a risk factor for rheumatoid arthritis

Cited by 25 publications

References 35 publications

STAT2*C related genotypes and allele but not TLR4 and CD40 gene polymorphisms are associated with higher susceptibility for asthma

STAT2*C related genotypes and allele but not TLR4 and CD40 gene polymorphisms are associated with higher susceptibility for asthma

<i>In vitro</i> anti-inflammatory and free radical scavenging activities of crude saponins extracted from <i>Albuca bracteata</i>Jacq. Bulb.

Influence of Endothelial Nitric Oxide Synthase Gene Intron-4 27bp Repeat Polymorphism on Its Expression in Autoimmune Diseases

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