Analysis of common transforming growth factor beta‐1 gene polymorphisms in gastric and duodenal ulcer disease: Pilot study

Polonikov, Alexey; Иванов, В. П.; Белугин, Д. А.; Khoroshaya, I. V.; Kolchanova, Inessa O; Солодилова, М. А.; Tutochkina, Margarita P; Stepchenko, Alexander A.

doi:10.1111/j.1440-1746.2006.04542.x

Cited by 16 publications

(10 citation statements)

References 40 publications

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“…These growth factors trigger mitogenic and survival pathways utilizing Ras, MAPK, PI-3K/Akt, PLC-␥, and Rho/Rac/actin signaling. TGF-␤ is well known as a multifunctional cytokine that regulates many biological processes, including cell proliferation, differentiation, adhesion, intercellular signaling, and the accumulation of extracellular matrix proteins and thus has an essential role during wound healing and tissue repair (23,24). Many studies over recent years have suggested that TGF-␤ plays a crucial role in both inflammation and tissue injury repair.…”

Section: Discussionmentioning

confidence: 99%

“…Many studies over recent years have suggested that TGF-␤ plays a crucial role in both inflammation and tissue injury repair. Polonikov et al (23) showed that TGF-␤ may play an essential role in peptic ulcer disease, and proposed that the biological effects of TGF-␤ 1 , an isoform of TGF-␤, are divided into four groups. Firstly, TGF-␤ 1 is likely to be needed to restrict local damage to the gastric mucosa after acute injury.…”

Section: Discussionmentioning

confidence: 99%

“…Thirdly, TGF-␤ 1 increases immunosuppression, and fourthly, TGF-␤ 1 repairs tissue injury and promotes ulcer healing. One of the properties of TGF-␤ 1 is its ability to induce fibrosis and promote the accumulation of the extracellular matrix (3,18,23,24). TGF-␤ 1 also induces fibroblast proliferation and stimulation of collagen synthesis, and it enhances extracellular matrix accumulation via the induction of CTGF (23,27).…”

Section: Discussionmentioning

confidence: 99%

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Role of microsomal prostaglandin E synthase-1 in the facilitation of angiogenesis and the healing of gastric ulcers

Ohno

Hattori

et al. 2010

American Journal of Physiology-Gastrointestinal and Liver Physi

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The importance of prostaglandin E(2) in various pathophysiological events emphasizes the necessity of understanding the role of PGE synthases (PGESs) in vivo. However, there has been no report on the functional relevance of microsomal PGES-1 (mPGES-1) to the physiological healing processes of gastric ulcers, or to angiogenesis, which is indispensable to the healing processes. In this report, we tested whether mPGES-1 plays a role in the healing of gastric ulcers and in the enhancement of angiogenesis using mPGES-1 knockout mice (mPGES-1 KO mice) and their wild-type (WT) counterparts. Gastric ulcers were induced by the serosal application of 100% acetic acid, and the areas of the ulcers were measured thereafter. mPGES-1 together with cyclooxygenase-2 were induced in the granulation tissues compared with normal stomach tissues. The healing of acetic acid-induced ulcers was significantly delayed in mPGES-1 KO mice compared with WT. This was accompanied with reduced angiogenesis in ulcer granulation tissues, as estimated by CD31 mRNA levels determined by real-time PCR and the microvessel density in granulation tissues. The mRNA levels of proangiogenic growth factors, such as transforming growth factor-β, basic fibroblast growth factor, and connective tissue growth factor in ulcer granulation tissues determined were reduced in mPGES-1 KO mice compared with WT. The present results suggest that mPGES-1 enhances the ulcer-healing processes and the angiogenesis indispensable to ulcer healing, and that a selective mPGES-1 inhibitor should be used with care in patients with gastric ulcers.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Role of microsomal prostaglandin E synthase-1 in the facilitation of angiogenesis and the healing of gastric ulcers

Ohno

Hattori

et al. 2010

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…The control group included blood donors, healthy volunteers and hospital-based patients (all subjects were recruited from the surgical, traumatic, and infectious divisions of Kursk hos pitals) with normal blood pressure and without cardiovas cular or other chronic diseases. The control group was recruited over the same periods of time [34][35][36][37][38]. To ensure an ethnically homogeneous population, only Russian resi dents living in Central Russia for at least two generations have been included in the study.…”

Section: Study Participantsmentioning

confidence: 99%

A comprehensive study revealed SNP–SNP interactions and a sex-dependent relationship between polymorphisms of the CYP2J2 gene and hypertension risk

et al. 2018

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This study investigated whether common polymorphisms of cytochrome P450 2J2 (CYP2J2), a major enzyme that controls the biosynthesis of vasoactive epoxyeicosatrienoic acids, are collectively involved in the molecular basis of essential hypertension (EH). A total of 2314 unrelated Russian subjects from the Kursk (discovery sample: 913 EH patients and 645 controls) and Belgorod (replication sample: 345 EH patients and 411 controls) regions were recruited for this study. Eight single nucleotide polymorphisms (SNPs), including rs890293, rs11572182, rs10493270, rs1155002, rs2280275, rs7515289, rs11572325, and rs10889162, of CYP2J2 were genotyped using the MassARRAY 4 system and TaqMan-based assays. Significant associations were identified among the SNPs rs890293 (OR = 2.17, 95%CI 1.30-3.65), rs2280275 (OR = 1.59, 95%CI 1.10-2.37) and rs11572325 (OR = 1.89, 95%CI 1.22-2.95) and the risk of EH in females from the Kursk population. Sixteen CYP2J2 genotype combinations only showed significant associations with EH risk only in females. A common haplotype, T-T-G-CC -C-T-A, increased the risk of EH in females. The bioinformatic analysis enabled identification of the SNPs that possess regulatory potential and/or are located within the binding sites for multiple transcription factors that play roles in the pathways involved in hypertension pathogenesis. Moreover, the polymorphisms rs890293, rs2280275, and rs11572325 were found to be significantly associated with hypertension risk in the Belgorod population. In conclusion, the rs2280275 and rs11572325 SNPs of CYP2J2 may be considered novel genetic markers of hypertension, at least in Russian women. However, sex-specific associations between CYP2J2 gene polymorphisms and hypertension require further investigation to clarify the specific genetic and/or environmental factors that are responsible for the increased disease susceptibility of women compared to that of men.

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“…The control group included blood donors, healthy volunteers as well as hospital-based patients recruited from surgical, traumatic, infectious divisions of Kursk hospitals without cardiovascular and other chronic diseases. The control group was recruited over several periods in the framework of our previous studies (Polonikov et al, 2007;Polonikov et al, 2008;Polonikov et al, 2009;Bushueva et al, 2014;Polonikov et al, 2015;Polonikov et al, 2017). Demographic and clinical characteristics of the study subjects are listed in Table 1.…”

Section: Study Participantsmentioning

confidence: 99%

Polymorphisms of CYP2C8 , CYP2C9 and CYP2C19 and risk of coronary heart disease in Russian population

Polonikov

Харченко

Bykanova

et al. 2017

Gene

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Epoxyeicosatrienoic acids (EETs) are important vasoactive products of arachidonic acid metabolism with a wide range of biological actions in the cardiovascular system. The present study investigated whether single nucleotide polymorphisms (SNP) of genes coding cytochrome P450 2C subfamily, enzymes involved in biosynthesis of EETs, are associated with the risk of coronary heart disease (CHD). A total of 1255 unrelated Russian subjects comprising 561 patients with angiographically diagnosed CHD and 694 age- and sex-matched healthy subjects were included in the study. DNA samples from all study participants were genotyped for six common SNPs rs7909236, rs1934953 of CYP2C8, rs9332242, rs4918758 and rs61886769 of CYP2C9 and rs4244285 of CYP2C19 using by the Mass-ARRAY 4 system. SNP rs4918758 of CYP2C9 was associated with decreased risk of CHD (codominant model) at a borderline significance with odds ratio adjusted for sex and age 0.61 (95% CI: 0.41-0.92, P=0.038, Q=0.20). SNP rs9332242 of CYP2C9 showed a trend towards association with increased CHD risk in cigarette smokers (P=0.049, Q=0.29). Log-likelihood ratio test (LRT) pointed out epistatic interactions between rs9332242 and rs61886769 of CYP2C9 (codominant model, P=0.02), however, this P-value did not survive after correction for multiple tests. Bioinformatic analysis revealed a regulatory potential for a majority of the investigated SNPs. Our preliminary results demonstrate that polymorphisms of genes encoding CYP2C subfamily represent potential genetic markers of CHD susceptibility. Further studies are required to substantiate the contribution of these genes to the disease risk.

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Analysis of common transforming growth factor beta‐1 gene polymorphisms in gastric and duodenal ulcer disease: Pilot study

Cited by 16 publications

References 40 publications

Role of microsomal prostaglandin E synthase-1 in the facilitation of angiogenesis and the healing of gastric ulcers

Role of microsomal prostaglandin E synthase-1 in the facilitation of angiogenesis and the healing of gastric ulcers

A comprehensive study revealed SNP–SNP interactions and a sex-dependent relationship between polymorphisms of the CYP2J2 gene and hypertension risk

Polymorphisms of CYP2C8 , CYP2C9 and CYP2C19 and risk of coronary heart disease in Russian population

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