Genetic contribution in gastroesophageal reflux disease

Doctoral Dissertation uoadl:2914812 12 Read counter

Faculty of Medicine
Library of the School of Health Sciences
Deposit date:
Argyrou Alexandra
Dissertation committee:
Δεληβελιώτης Χαράλαμπος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Θεοδοσόπουλος Θεοδόσιος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Γκιόκας Γεώργιος, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ, Επιβλέπων
Παπακωνσταντίνου Ιωάννης, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Καραμανώλης Γεώργιος, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Δάφνιος Νικόλαος, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Γαζούλη Μαρία, Αναπληρώτρια Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Original Title:
Γενετική διερεύνηση της γαστροοισοφαγικής παλινδρόμησης
Translated title:
Genetic contribution in gastroesophageal reflux disease
Gastroesophageal reflux disease (GERD) represents a common gastrointestinal disorder, having a substantial impact on the patients’ quality of life, as well as the health system. The prevalence of the disease is estimated up to 20% in the Western World and <5% in Asia. Various GERD risk factors have been identified and evaluated over the years, including a significant number of genetic factors. Genetic contribution appears to play an important role in the occurrence of GERD and GERD-related disorders such as Barrett's esophagus and esophageal adenocarcinoma. Twin and family studies have revealed about 31% heredity of the disease. Numerous single-nucleotide polymorphisms (SNPs) in various genes, such as the FOXF1, MHC, CCND1, anti-inflammatory cytokine genes and DNA repair genes have been strongly associated with an increased risk of GERD. GERD, Barrett's esophagus, and esophageal adenocarcinoma share several genetic loci. Despite the polygenic basis of GCRD, specific genetic loci, such as rs10419226 on chromosome 19, rs2687201 on chromosome 3, rs10852151 on chromosome 15 and rs520525 on the PRRX1 gene, have been reported as potential risk factors. According to many studies, the BARX1 and ADAMTS17 genes have been suggested as genetic risk loci for the development of GERD and its complications. The purpose of this study is to investigate the potential association between the disease and BARX1 and ADAMTS17 polymorphisms in the Greek population. Total peripheral blood samples were collected from 160 GERD patients with and from 180 healthy control subjects. The Polymerase Chain Reaction (PCR) method was used to identify the two polymorphisms of BARX1 and ADAMTS17 (rs11789015 and rs4965272 respectively) and their possible association with GERD was investigated. From the data analysis, the rs11789015 AG and GG genotypes, as well as the G allele, were found to be significantly associated with GERD. Concerning the rs4965272 polymorphism, only the GG genotype was significantly associated with GERD. Consequently, a significant correlation between both polymorphisms and the disease is demonstrated. These findings suggest that esophageal differentiation or altered regulation on microfibrils in the cell environment could be implicated as possible mechanisms in the pathogenesis of GERD. Further evaluation of the precise function and role of these two genes in the disease could suggest them as biomarkers, for the diagnosis of GERD and the selection of high risk patients. In addition, new gene / genetic therapies could be proposed in this increasingly common disease.
Main subject category:
Health Sciences
ADAMTS17, BARX1, Gastroesophageal reflux, Polymorphism, Genetic
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