Angiotensin II Type 1 Receptor rs5186 Gene Variant Predicts Incident NAFLD and Associated Hypertension: Role of Dietary Fat-Induced Pro-Inflammatory Cell Activation

Musso, Giovanni; Saba, Francesca; Cassader, Maurizio; Paschetta, Elena; Michieli, Franco De; Pinach, Silvia; Framarin, L.; Berrutti, M; Leone, Nicola; Parente, Renato; Khajekini, Mohammad Taghi Ayoubi; Zarovska, Adriana; Gambino, Roberto

doi:10.14309/ajg.0000000000000154

Cited by 26 publications

(17 citation statements)

References 51 publications

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“…In addition, rs2285666 SNP, has been recently related to a lower COVID-19 infection as well as case-fatality rate among Indian populations [19]. The rs5186 (C) allele in AGTR1 is associated with increased risk for essential hypertension [20,21]. Age and gender may also influence risk of AGTR1 SNPs and their role in hypertension and related disorders [22].…”

Section: Snps In Genes Of Renin-angiotensin System Included In the Studymentioning

confidence: 99%

Polymorphisms in ACE, ACE2, AGTR1 genes and severity of COVID-19 disease

et al. 2022

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Background Infection by the SARS-Cov-2 virus produces in humans a disease of highly variable and unpredictable severity. The presence of frequent genetic single nucleotide polymorphisms (SNPs) in the population might lead to a greater susceptibility to infection or an exaggerated inflammatory response. SARS-CoV-2 requires the presence of the ACE2 protein to enter in the cell and ACE2 is a regulator of the renin-angiotensin system. Accordingly, we studied the associations between 8 SNPs from AGTR1, ACE2 and ACE genes and the severity of the disease produced by the SARS-Cov-2 virus. Methods 318 (aged 59.6±17.3 years, males 62.6%) COVID-19 patients were grouped based on the severity of symptoms: Outpatients (n = 104, 32.7%), hospitalized on the wards (n = 73, 23.0%), Intensive Care Unit (ICU) (n = 84, 26.4%) and deceased (n = 57, 17.9%). Comorbidity data (diabetes, hypertension, obesity, lung disease and cancer) were collected for adjustment. Genotype distribution of 8 selected SNPs among the severity groups was analyzed. Results Four SNPs in ACE2 were associated with the severity of disease. While rs2074192 andrs1978124showed a protector effectassuming an overdominant model of inheritance (G/A vs. GG-AA, OR = 0.32, 95%CI = 0.12–0.82; p = 0.016 and A/G vs. AA-GG, OR = 0.37, 95%CI: 0.14–0.96; p = 0.038, respectively); the SNPs rs2106809 and rs2285666were associated with an increased risk of being hospitalized and a severity course of the disease with recessive models of inheritance (C/C vs. T/C-T/T, OR = 11.41, 95% CI: 1.12–115.91; p = 0.012) and (A/A vs. GG-G/A, OR = 12.61, 95% CI: 1.26–125.87; p = 0.0081). As expected, an older age (OR = 1.47), male gender (OR = 1.98) and comorbidities (OR = 2.52) increased the risk of being admitted to ICU or death vs more benign outpatient course. Multivariable analysis demonstrated the role of the certain genotypes (ACE2) with the severity of COVID-19 (OR: 0.31, OR 0.37 for rs2074192 and rs1978124, and OR = 2.67, OR = 2.70 for rs2106809 and rs2285666, respectively). Hardy-Weinberg equilibrium in hospitalized group for I/D SNP in ACE was not showed (p<0.05), which might be due to the association with the disease. No association between COVID-19 disease and the different AGTR1 SNPs was evidenced on multivariable, nevertheless the A/A genotype for rs5183 showed an higher hospitalization risk in patients with comorbidities. Conclusions Different genetic variants in ACE2 were associated with a severe clinical course and death groups of patients with COVID-19. ACE2 common SNPs in the population might modulate severity of COVID-19 infection independently of other known markers like gender, age and comorbidities.

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Section: Snps In Genes Of Renin-angiotensin System Included In the Studymentioning

confidence: 99%

Polymorphisms in ACE, ACE2, AGTR1 genes and severity of COVID-19 disease

et al. 2022

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“…Bioinformatic analysis revealed that the AGTR1 (angiotensin receptor type 1) gene, also connected with H. pylori infection and MetS [196,197], might be involved in several signaling pathways connected with the development of NAFLD [198]. In a recent prospective cohort study, the gain-of-function A1166C (rs5186) variant in the AGTR1 gene represented a strong predictor of incident NAFLD and related arterial hypertension [199]. Thus, despite the previous unsuccessful clinical trial of angiotensin receptor blockers in managing fibrosis in NAFLD patients [200], patients with the AGTR1 A1166C variant may exhibit a subtype of NAFLD that may benefit more from the personalized usage of angiotensin receptor blockers.…”

Section: Hypertension 5 H Pylori and Mets-related Nafld May Promote Arterial Hypertension By Increasing Vasoconstriction And Decreasing Vmentioning

confidence: 99%

Impact of Helicobacter pylori-Related Metabolic Syndrome Parameters on Arterial Hypertension

et al. 2021

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Arterial hypertension is a risk factor for several pathologies, mainly including cardio-cerebrovascular diseases, which rank as leading causes of morbidity and mortality worldwide. Arterial hypertension also constitutes a fundamental component of the metabolic syndrome. Helicobacter pylori infection is one of the most common types of chronic infection globally and displays a plethora of both gastric and extragastric effects. Among other entities, Helicobacter pylori has been implicated in the pathogenesis of the metabolic syndrome. Within this review, we illustrate the current state-of-the-art evidence, which may link several components of the Helicobacter pylori-related metabolic syndrome, including non-alcoholic fatty liver disease and arterial hypertension. In particular, current knowledge of how Helicobacter pylori exerts its virulence through dietary, inflammatory and metabolic pathways will be discussed. Although there is still no causative link between these entities, the emerging evidence from both basic and clinical research supports the proposal that several components of the Helicobacter pylori infection-related metabolic syndrome present an important risk factor in the development of arterial hypertension. The triad of Helicobacter pylori infection, the metabolic syndrome, and hypertension represents a crucial worldwide health problem on a pandemic scale with high morbidity and mortality, like COVID-19, thereby requiring awareness and appropriate management on a global scale.

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“…In a recent prospective cohort study, the gain-of function A1166C (rs5186) variant in the AGTR1 gene represented a strong predictor for incident NAFLD and associated hypertension. In addition, polymorphism in AGTR1 may influence the risk of liver fibrosis in NAFLD [56].…”

Section: Genetic and Epigenetic Modificationsmentioning

confidence: 99%

Non-Alcoholic Fatty Liver Disease and Cardiovascular Comorbidities: Pathophysiological Links, Diagnosis, and Therapeutic Management

et al. 2021

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Non-alcoholic fatty liver disease (NAFLD) has a growing prevalence in recent years. Its association with cardiovascular disease has been intensively studied, and certain correlations have been identified. The connection between these two entities has lately aroused interest regarding therapeutic management. In order to find the best therapeutic options, a detailed understanding of the pathophysiology that links (NAFLD) to cardiovascular comorbidities is needed. This review focuses on the pathogenic mechanisms that are behind these two diseases and on the therapeutic management available at this time.

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Angiotensin II Type 1 Receptor rs5186 Gene Variant Predicts Incident NAFLD and Associated Hypertension: Role of Dietary Fat-Induced Pro-Inflammatory Cell Activation

Cited by 26 publications

References 51 publications

Polymorphisms in ACE, ACE2, AGTR1 genes and severity of COVID-19 disease

Polymorphisms in ACE, ACE2, AGTR1 genes and severity of COVID-19 disease

Impact of Helicobacter pylori-Related Metabolic Syndrome Parameters on Arterial Hypertension

Non-Alcoholic Fatty Liver Disease and Cardiovascular Comorbidities: Pathophysiological Links, Diagnosis, and Therapeutic Management

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