Association of <i>Helicobacter pylori</i> with Serum HIF-1α, HIF-2α, and Human Transmembrane Prolyl 4-Hydroxylase Activity in Patients with Chronic Gastritis

<i>Background and Objectives</i>: Chronic mucosal infection with <i>Helicobacter pylori</i> (<i>H. pylori</i>) plays a key role in the development of gastroduodenal disorders such as chronic gastritis, peptic ulcers, gastric lymphoma, and gastric cancer by trigger...

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Main Authors: Sefa Ergün, Fadime Kutluk, Basar Can Turgut, Seyma Dumur, Uğurcan Sayılı, Dilek Duzgun Ergun, Hafize Uzun
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Language:English
Published: MDPI AG 2025-06-01
Series:Medicina
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Online Access:https://www.mdpi.com/1648-9144/61/7/1174
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author Sefa Ergün
Fadime Kutluk
Basar Can Turgut
Seyma Dumur
Uğurcan Sayılı
Dilek Duzgun Ergun
Hafize Uzun
author_facet Sefa Ergün
Fadime Kutluk
Basar Can Turgut
Seyma Dumur
Uğurcan Sayılı
Dilek Duzgun Ergun
Hafize Uzun
author_sort Sefa Ergün
collection DOAJ
description <i>Background and Objectives</i>: Chronic mucosal infection with <i>Helicobacter pylori</i> (<i>H. pylori</i>) plays a key role in the development of gastroduodenal disorders such as chronic gastritis, peptic ulcers, gastric lymphoma, and gastric cancer by triggering local immune responses and inducing hypoxic and inflammatory conditions in the gastric mucosa. This study aims to evaluate the potential diagnostic value of hypoxia-inducible factors HIF-1α and HIF-2α, along with transmembrane prolyl 4-hydroxylase (P4H-TM), as biomarkers in <i>H. pylori</i>-positive patients. Additionally, the study investigates the association between these markers and alterations in lipid profiles, as well as their involvement in the molecular mechanisms underlying gastric conditions like gastritis, particularly in the context of H. pylori infection. <i>Materials and Methods</i>: This study was conducted at Istanbul Avcılar Murat Kölük State Hospital’s General Surgery Outpatient Clinic. A total of 60 participants were included: 40 patients diagnosed with chronic gastritis (20 <i>H. pylori</i>-positive and 20 <i>H. pylori</i>-negative) and 20 healthy controls confirmed negative by 13C-urea breath test. Blood samples were collected for ELISA analysis of HIF-1α, HIF-2α, and P4H-TM levels. Additionally, lipid profiles were measured and compared among the groups. <i>Results:</i> No significant differences were found among the groups in terms of demographic factors such as age, sex, or body mass index (BMI). However, significant variations were observed in the levels of HIF-1α, HIF-2α, and P4H-TM across all groups (<i>p</i> < 0.001 for each marker). These markers were substantially elevated in the <i>H. pylori</i>-positive gastritis group compared to both the H. pylori-negative and healthy control groups. Receiver Operating Characteristic (ROC) curve analysis revealed that all evaluated markers exhibited strong diagnostic accuracy in differentiating H. pylori-positive individuals from other groups. HIF-1α (AUC: 0.983) and HIF-2α (AUC: 0.981) both achieved 100% sensitivity with specificities of 93.3% and 91.1%, respectively. P4H-TM showed an AUC of 0.927, with 85% sensitivity and 95.6% specificity. <i>Conclusions:</i> These findings indicate that HIF-1α, HIF-2α, and P4H-TM may serve as effective biomarkers for diagnosing <i>H. pylori</i>-positive patients and may be linked to changes in lipid metabolism. The elevated expression of these markers in response to <i>H. pylori</i> infection highlights their potential roles in the inflammatory and hypoxic pathways that contribute to the pathogenesis of gastric diseases such as gastritis.
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spelling doaj-art-5e26c1b48aa744a7af0a1337a7f48a9c2025-07-25T13:29:20ZengMDPI AGMedicina1010-660X1648-91442025-06-01617117410.3390/medicina61071174Association of <i>Helicobacter pylori</i> with Serum HIF-1α, HIF-2α, and Human Transmembrane Prolyl 4-Hydroxylase Activity in Patients with Chronic GastritisSefa Ergün0Fadime Kutluk1Basar Can Turgut2Seyma Dumur3Uğurcan Sayılı4Dilek Duzgun Ergun5Hafize Uzun6Department of General Surgery, Cerrahpaşa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul 34320, TurkeyDepartment of General Surgery, Binali Yildirim University Mengücek Gazi Training and Research Hospital, Erzincan 24100, TurkeyDepartment of General Surgery, Istanbul Training and Research Hospital, University of Health Sciences, Istanbul 34098, TurkeyDepartment of Medical Biochemistry, Faculty of Medicine, İstanbul Atlas University, Istanbul 34403, TurkeyDepartment of Public Health, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul 34320, TurkeyDepartment of Biophysics, Faculty of Medicine, Istanbul Aydin University, Istanbul 34513, TurkeyDepartment of Medical Biochemistry, Faculty of Medicine, İstanbul Atlas University, Istanbul 34403, Turkey<i>Background and Objectives</i>: Chronic mucosal infection with <i>Helicobacter pylori</i> (<i>H. pylori</i>) plays a key role in the development of gastroduodenal disorders such as chronic gastritis, peptic ulcers, gastric lymphoma, and gastric cancer by triggering local immune responses and inducing hypoxic and inflammatory conditions in the gastric mucosa. This study aims to evaluate the potential diagnostic value of hypoxia-inducible factors HIF-1α and HIF-2α, along with transmembrane prolyl 4-hydroxylase (P4H-TM), as biomarkers in <i>H. pylori</i>-positive patients. Additionally, the study investigates the association between these markers and alterations in lipid profiles, as well as their involvement in the molecular mechanisms underlying gastric conditions like gastritis, particularly in the context of H. pylori infection. <i>Materials and Methods</i>: This study was conducted at Istanbul Avcılar Murat Kölük State Hospital’s General Surgery Outpatient Clinic. A total of 60 participants were included: 40 patients diagnosed with chronic gastritis (20 <i>H. pylori</i>-positive and 20 <i>H. pylori</i>-negative) and 20 healthy controls confirmed negative by 13C-urea breath test. Blood samples were collected for ELISA analysis of HIF-1α, HIF-2α, and P4H-TM levels. Additionally, lipid profiles were measured and compared among the groups. <i>Results:</i> No significant differences were found among the groups in terms of demographic factors such as age, sex, or body mass index (BMI). However, significant variations were observed in the levels of HIF-1α, HIF-2α, and P4H-TM across all groups (<i>p</i> < 0.001 for each marker). These markers were substantially elevated in the <i>H. pylori</i>-positive gastritis group compared to both the H. pylori-negative and healthy control groups. Receiver Operating Characteristic (ROC) curve analysis revealed that all evaluated markers exhibited strong diagnostic accuracy in differentiating H. pylori-positive individuals from other groups. HIF-1α (AUC: 0.983) and HIF-2α (AUC: 0.981) both achieved 100% sensitivity with specificities of 93.3% and 91.1%, respectively. P4H-TM showed an AUC of 0.927, with 85% sensitivity and 95.6% specificity. <i>Conclusions:</i> These findings indicate that HIF-1α, HIF-2α, and P4H-TM may serve as effective biomarkers for diagnosing <i>H. pylori</i>-positive patients and may be linked to changes in lipid metabolism. The elevated expression of these markers in response to <i>H. pylori</i> infection highlights their potential roles in the inflammatory and hypoxic pathways that contribute to the pathogenesis of gastric diseases such as gastritis.https://www.mdpi.com/1648-9144/61/7/1174gastritis<i>Helicobacter pylori</i>hypoxia-inducible factor-1αHIF-2αlipid profiletransmembrane prolyl 4-hydroxylase
spellingShingle Sefa Ergün
Fadime Kutluk
Basar Can Turgut
Seyma Dumur
Uğurcan Sayılı
Dilek Duzgun Ergun
Hafize Uzun
Association of <i>Helicobacter pylori</i> with Serum HIF-1α, HIF-2α, and Human Transmembrane Prolyl 4-Hydroxylase Activity in Patients with Chronic Gastritis
Medicina
gastritis
<i>Helicobacter pylori</i>
hypoxia-inducible factor-1α
HIF-2α
lipid profile
transmembrane prolyl 4-hydroxylase
title Association of <i>Helicobacter pylori</i> with Serum HIF-1α, HIF-2α, and Human Transmembrane Prolyl 4-Hydroxylase Activity in Patients with Chronic Gastritis
title_full Association of <i>Helicobacter pylori</i> with Serum HIF-1α, HIF-2α, and Human Transmembrane Prolyl 4-Hydroxylase Activity in Patients with Chronic Gastritis
title_fullStr Association of <i>Helicobacter pylori</i> with Serum HIF-1α, HIF-2α, and Human Transmembrane Prolyl 4-Hydroxylase Activity in Patients with Chronic Gastritis
title_full_unstemmed Association of <i>Helicobacter pylori</i> with Serum HIF-1α, HIF-2α, and Human Transmembrane Prolyl 4-Hydroxylase Activity in Patients with Chronic Gastritis
title_short Association of <i>Helicobacter pylori</i> with Serum HIF-1α, HIF-2α, and Human Transmembrane Prolyl 4-Hydroxylase Activity in Patients with Chronic Gastritis
title_sort association of i helicobacter pylori i with serum hif 1α hif 2α and human transmembrane prolyl 4 hydroxylase activity in patients with chronic gastritis
topic gastritis
<i>Helicobacter pylori</i>
hypoxia-inducible factor-1α
HIF-2α
lipid profile
transmembrane prolyl 4-hydroxylase
url https://www.mdpi.com/1648-9144/61/7/1174
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