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Risk factors for gastroesophageal reflux disease and analysis of genetic contributors

World Journal of Clinical Cases 2018年第8期6卷 176-182页

作者： Alexandra Argyrou Evangelia Legaki Christos Koutserimpas Maria Gazouli Ioannis Papaconstantinou george Gkiokas george karamanolis Department of Basic Medical Sciences Laboratory of BiologySchool of MedicineNational and Kapodistrian University of Athens 2nd Department of General Surgery "Sismanoglion" General Hospital of Athens 2nd Department of Surgery School of MedicineNational and Kapodistrian University of Athens Gastroenterology Unit 2nd Department of SurgerySchool of MedicineNational and Kapodistrian University of Athens

Gastroesophageal reflux disease(GERD) is a common gastrointestinal disorder with an increasing prevalence. GERD develops when the reflux of stomach contents causes troublesome typical and atypical symptoms and/or complications. Several risk factors of GERD have been identified and evaluated over the years, including a considerable amount of genetic factors. Multiple mechanisms are involved in the pathogenesis of GERD including:(1) motor abnormalities, such as impaired lower esophageal sphincter(LES) resting tone, transient LES relaxations, impaired esophageal acid clearance and delayed gastric emptying; and(2) anatomical factors, such as hiatal hernia and obesity. Genetic contribution seems to play a major role in GERD and GERD-related disorders development such Barrett's esophagus and esophageal adenocarcinoma. Twin and family studies have revealed an about 31% heritability of the disease. Numerous single-nucleotide polymorphisms in various genes like FOXF1, MHC, CCND1, anti-inflammatory cytokine and DNA repair genes have been strongly associated with increased GERD risk. GERD, Barrett'sesophagus and esophageal adenocarcinoma share several genetic loci. Despite GERD polygenic basis,specific genetic loci such as rs10419226 on chromosome 19, rs2687201 on chromosome 3, rs10852151 on chromosome 15 and rs520525 on the paired related homeobox 1 gene have been mentioned as potential risk factors. Further investigation on the risk genes may elucidate their exact function and role and demonstrate new therapeutic approaches to this increasingly common disease.

关键词： Single nucleotide polymorphisms Genetic risk loci Risk factors Gastroesophageal reflux disease Gastroesophageal reflux disease development

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Gene polymorphisms associated with functional dyspepsia

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World Journal of Gastroenterology 2015年第25期21卷 7672-7682页

作者： Anastasia Kourikou george P karamanolis george D Dimitriadis Konstantinos Triantafyllou Hepatogastroenterology Unit Second Department of Internal Medicine and Research Institute Attikon University General Hospital Medical School Athens University Academic Department of Gastro- enterology Laiko General Hospital

Functional dyspepsia(FD) is a constellation of functional upper abdominal complaints with poorly elucidated pathophysiology. However, there is increasing evidence that susceptibility to FD is influenced by hereditary factors. Genetic association studies in FD have examined genotypes related to gastrointestinal motility or sensation, as well as those related to inflammation or immune response. G-protein b3 subunit gene polymorphisms were first reported as being associated with FD. Thereafter, several gene polymorphisms including serotonin transporter promoter, interlukin-17 F, migration inhibitory factor, cholecystocynine-1 intron 1, cyclooxygenase-1, catechol-o-methyltransferase, transient receptor potential vanilloid 1 receptor, regulated upon activation normal T cell expressed and secreted, p22 PHOX, Toll like receptor 2, SCN10 A, CD14 and adrenoreceptors have been investigated in relation to FD; however, the results are contradictory. Several limitations underscore the value of current studies. Among others, inconsistencies in the definitions of FD and controls, subject composition differences regarding FD subtypes, inadequate samples, geographical and ethnical differences, as well as unadjusted environmental factors. Further well-designed studies are necessary to determine how targeted genes polymorphisms, influence the clinical manifestations and potentially the therapeutic response in FD.

关键词： Functional dyspepsia Gene polymorphism Genetic susceptibility Pathophysiology

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Colonic gas explosion during therapeutic colonoscopy with electrocautery

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World Journal of Gastroenterology 2007年第40期13卷 5295-5298页

作者： Spiros D Ladas george karamanolis Emmanuel Ben-Soussan Hepatogastroenterology Unit 2~(nd) Department of Internal Medicine-PropaedeuticMedical SchoolAthens University"Attikon"University General HospitalAthensGreece Clinique de I'Alma 166 rue de I'université 750007ParisFrance

Therapeutic colonoscopy with electrocautery is widely used around the world. Adequate colonic cleansing is considered a crucial factor for the safety of this procedure. Colonic gas explosion, although rare, is one of the most frightening iatrogenic complications during colonoscopy with electrocautery. This complication is the result of an accumulation of colonic gases to explosive concentrations, but may be prevented by meticulous bowel preparation. The purpose *** review is to discuss the indications and the types of bowel preparations for therapeutic colonoscopy, and to contribute recommendations for the adequate bowel preparation for colonoscopy with electrocautery.

关键词： Colonic gas explosion Electrocautery Therapeutic polypectomy Argon plasma coagulation Polypectomy

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Endoscopic treatments for chronic radiation proctitis

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World Journal of Gastrointestinal Endoscopy 2013年第7期5卷 308-312页

作者： george karamanolis Panagiota Psatha Konstantinos Triantafyllou Gastroenterology Unit 2nd Department of Surgery "Aretaieio" University Hospital Athens University11528 Athens Greece Hepatogastroenterology Unit 2nd Department of Internal Medicine and Research Institute "Attikon" University General Hospital Athens University12462 Athens Greece

Chronic radiation proctitis is a complication that occurs in patients who receive radiation therapy for pelvic malignancies. The common presentation is with rectal bleeding, but also rectal pain, diarrhea, tenesmus and even passage of mucus can occur. The optimal treatment of bleeding due to radiation proctitis remains unclear. Among various therapeutic options, medical management is generally ineffective and surgical intervention has a high incidence of morbidity. Promising advances have been made in endoscopic therapy, including argon plasma coagulation (APC), formalin application as well as new techniques such as radio-frequency ablation and cryoablation. APC is a safe, highly effective and long-lasting therapy in patients with rectal bleeding associated with radiation proctitis. It has been shown that several sessions of APC reduce the rate of bleeding and therefore the blood transfusion requirements. Moreover, the effect of treatment is long lasting. However, best results are achieved in patients with mild to moderate radiation proctitis, leaving space for alternative treatments for patients with more severe disease. In patients with severe or refractoryradiation proctitis intra rectal formalin application is an appropriate treatment option. Radiofrequency ablation and cryoablation have shown efficacy as alternative methods in a limited number of patients with refractory chronic radiation proctitis.

关键词： Radiation proctitis Endoscopic treatment Argon plasma coagulation Formalin application Cryoablation Radiofrequency ablation

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Association of miR-146 rs2910164,miR-196a rs11614913,miR-221 rs113054794 and miR-224 rs188519172 polymorphisms with anti-TNF treatment response in a Greek population with Crohn's disease

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World Journal of Gastrointestinal Pharmacology and Therapeutics 2017年第4期8卷 193-200页

作者： Ioannis Papaconstantinou Christina Kapizioni Evangelia Legaki Elena Xourgia george karamanolis Antonios Gklavas Maria Gazouli 2^nd Department of Surgery Aretaieio HospitalMedical SchoolNational and Kapodistrian University of Athens Gastroenterology Department Tzaneion General Hospital Laboratory of Biology Medical SchoolNational and Kapodistrian University of Athens Gastroenterology Unit 2^nd Department of SurgeryAretaieio HospitalMedical SchoolNational and Kapodistrian University of Athens

AIM To investigate the correlation between rs2910164, rs11 614913, rs113054794, and rs188519172 polymorphisms and response to anti-TNF treatment in patients with Crohn's disease(CD). METHODS One hundred seven patients with CD based on standardclinical, endoscopic, radiological, and pathological criteria were included in the study. They all received infliximab or adalimumab intravenously or subcutaneously at standard induction doses as per international guidelines. Clinical and biochemical response was assessed using the HarveyBradshaw index and CRP levels respectively. Endoscopic response was evaluated by ileocolonoscopy at week 12-20 of therapy. The changes in endoscopic appearance compared to baseline were classified into four categories, and patients were classified as responders and nonresponders. Whole peripheral blood was extracted and genotyping was performed by *** One hundred and seven patients were included in the study. Seventy two(67.3%) patients were classified as complete responders, 22(20.5%) as partial while 13(12.1%) were primary non-responders. No correlation was detected between response to anti-TNF agents and patients' characteristics such as gender, age and disease duration while clinical and biochemical indexes used were associated with endoscopic response. Concerning prevalence of rs2910164, rs11614913, and rs188519172 polymorphisms of miR-146, miR-196a and miR-224 respectively no statistically important difference was found between complete, partial, and non-responders to antiTNF treatment. Actually CC genotype of rs2910164 was not detected in any patient. Regarding rs113054794 of miR-221, normal CC genotype was the only one detected in all studied patients, suggesting this polymorphism is highly rare in the studied *** No correlation is detected between studied polymorphisms and patients' response to anti-TNF treatment. Polymorphism rs113054794 is not detected in our population.

关键词： MicroRNA Crohn’s disease Polymorphisms Anti-TNF Biomarkers

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Molecular basis of the irritable bowel syndrome

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World Journal of Gastroenterology 2014年第2期20卷 376-383页

作者： Anna Vaiopoulou Georgios karamanolis Theodora Psaltopoulou george Karatzias Maria Gazouli Department of Basic Medical Science Laboratory of BiologySchool of MedicineUniversity of Athens11527 AthensGreece 2~(nd) Department of Surgery "Aretaieio" University HospitalSchool of MedicineUniversity of Athens11527 AthensGreece Department of Hygiene Epidemiology and Medical StatisticsSchool of MedicineUniversity of Athens11527 AthensGreece

Irritable bowel syndrome(IBS)is a functional disorder characterized by abdominal pain,discomfort and *** pathophysiology of IBS is poorly understood,but the presence of psychosocial basis is now *** is an increasing number of publications supporting the role of genetics in *** of the variations are found in genes associated with the brain-gut axis,revealing the strong correlation of brain-gut axis and ***,which play critical roles in physiological processes,are not well studied in ***,so far there is found an involvement of alterations in miRNA expression or sequence,in IBS *** phenotype is affected by epigenetic alteration and *** in DNA and histone methylation are observed in patients who suffered childhood trauma or abuse,resulting in altered gene expression,such as the glucocorticoid receptor ***,diet is another factor associated with IBS,which may contribute to symptom *** foods may affect on bacterial metabolism and epigenetic modifications,predisposing to IBS.

关键词： Irritable bowel syndrome Gastrointestinal diseases Genetics Epigenetics Diet

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Association of rs1568885, rs1813443 and rs4411591 polymorphisms with anti-TNF medication response in Greek patients with Crohn's disease

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World Journal of Gastroenterology 2014年第13期20卷 3609-3614页

作者： Diamantis Thomas Maria Gazouli Theodoros Karantanos Stella Rigoglou Georgios karamanolis Konstantinos Bramis george Zografos george E Theodoropoulos Colorectal Unit 1st Department of Propaedeutic Surgery"Hippokrateio" HospitalSchool of MedicineUniversity of Athens11527 AthensGreece Department of Basic Medical Science Laboratory of BiologySchool of MedicineUniversity of Athens11527 AthensGreece Gastroenterology Unit 2nd Department of Surgery"Aretaieio" HospitalUniversity of AthensAthens 11527Greece

AIM: To investigate the correlation between rs1568885, rs1813443 and rs4411591 polymorphisms and response to infliximab in a cohort of Greek patients with Crohn’s disease (CD).

关键词： Crohn’ s disease, Treatment response, Infliximab, Polymorphisms

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Serum zonulin levels in patients with liver cirrhosis:Prognostic implications

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World Journal of Hepatology 2021年第10期13卷 1394-1404页

作者： Theodoros A Voulgaris Dimitrios Karagiannakis E Hadziyannis Spilios Manolakopoulos Georgios P karamanolis george Papatheodoridis John Vlachogiannakos Academic Department of Gastroenterology and Hepatology Medical School of National and Kapodistrian University of AthensGeneral Hospital of Athens“Laiko”Athens 11527Greece Academic Department of Medicine Hippokrat General HospitalNational and Kapodistrian University of AthensAthens 11527Greece

BACKGROUND Increased gut permeability and bacterial translocation play an important role in liver *** is a recently recognized protein involved in the disintegration of the intestinal *** To investigate possible differences in serum zonulin levels among patients with different cirrhosis stages and their potential prognostic *** Consecutive cirrhotic patients who attended our liver clinic were included in the *** zonulin levels,clinical,radiological and biochemical data were collected at *** who accepted participation in a regular surveillance program were followed-up for at least 12 *** We enrolled 116 cirrhotics[mean Child-Turcotte-Pugh(CTP)score:6.2±1.6;model for end-stage liver disease score:11±3.9].The causes of cirrhosis were viral hepatitis(39%),alcohol(30%),non-alcoholic fatty liver disease(17%),and other(14%).At baseline,53% had decompensated cirrhosis,48% had ascites,and 32% had history of hepatic *** zonulin levels were significantly higher in patients with CTP-B class than CTP-A class(4.2±2.4 ng/dL vs 3.5±0.9 ng/dL,P=0.038),with than without ascites(P=0.006),and with than without history of encephalopathy(P=0.011).Baseline serum zonulin levels were independently associated with the probability of decompensation at 1 year(P=0.039),with an area under the receiving operating characteristic of 0.723 for predicting hepatic *** CTP score(P=0.021)and portal vein diameter(P=0.022)were independent predictors of *** Serum zonulin levels are higher in patients with more advanced chronic liver disease and have significant prognostic value in identifying patients who will develop decompensation.

关键词： Zonulin Cirrhosis Intestinal barrier Bacterial translocation Decompensation Permeability

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