Influence of CYP2C19 genetic polymorphisms on clinical outcomes of intracranial aneurysms treated with stent-assisted coiling

2016 ◽  
Vol 9 (10) ◽  
pp. 958-962 ◽  
Author(s):  
Huijian Ge ◽  
Xianli Lv ◽  
Hui Ren ◽  
Hengwei Jin ◽  
Yuhua Jiang ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Genetic Polymorphisms ◽  
Intracranial Aneurysms ◽  
Loss Of Function ◽  
Bleeding Events ◽  
Clopidogrel Resistance ◽  
Increased Risk ◽  
Posterior Circulation Aneurysms ◽  
Cerebral Ischemic ◽  
Ischemic Events

ObjectiveTo investigate the influence of CYP2C19 genetic polymorphisms on clinical outcomes of intracranial aneurysms treated with stent-assisted coiling.MethodsBetween September 2014 and October 2015, we prospectively recruited 215 patients with intracranial aneurysms who were treated with stent-assisted coiling. CYP2C19 genotypes were determined and clopidogrel response was tested. The primary endpoints included symptomatic or silent ischemic events, and bleeding events. The secondary endpoint was clinical outcome at 3 months.ResultsOf the 215 patients, 108 (50.2%) were classified as intermediate metabolizers (IMs, CYP2C19*1/*2, *1/*3), 76 (35.3%) as extensive metabolizers (EMs, CYP2C19*1/*1) and 31 (14.4%) as poor metabolizers (PMs, CYP2C19*2/*2, *2/*3, *3/*3). Carriers of CYP2C19 loss-of-function (LOF) alleles (*2 or *3, p=0.001), especially PMs (p=0.004), had an increased risk for clopidogrel resistance. After the procedures, cerebral ischemic events occurred in 69 patients (32.1%) and bleeding was seen in 20 patients (9.3%). In comparison with IMs and PMs, EMs had a lower risk for ischemic events (21.1% vs 37.0% and 41.9%, p=0.02 and 0.027, respectively) and a relatively higher risk for bleeding events (18.4% vs 5.6% and 0%, p=0.006 and 0.01, respectively). Based on multivariate analysis, the carriage of CYP2C19 LOF alleles (p=0.032) and clopidogrel resistance (p=0.047) were considered as predictors of cerebral ischemic events, and EMs were significantly associated with bleeding (p=0.002). Posterior circulation aneurysms (p=0.038), hemorrhagic history (p=0.001) and poor metabolic genotypes (p=0.001) could result in poor clinical outcomes (modified Rankin Scale >2).ConclusionsCYP2C19 genetic polymorphisms had significant influence on the antiplatelet effect of clopidogrel, and could be considered as risk factors of ischemic or bleeding events and even clinical outcomes of patients with intracranial aneurysms treated with stent-assisted coiling.

scholarly journals Influence of Genetic Polymorphisms in P2Y12 Receptor Signaling Pathway on Antiplatelet Response to Clopidogrel in Coronary Heart Disease

2021 ◽  
Author(s):  
Dongjie Li ◽  
Yanjiao Zhang ◽  
Zhongyi Li ◽  
Xiaolei Hu ◽  
He Li ◽  
...  
Keyword(s):  
Genetic Polymorphisms ◽  
Interindividual Variability ◽  
Signal Pathway ◽  
Loss Of Function ◽  
Platelet Activity ◽  
Clopidogrel Resistance ◽  
Reaction Index ◽  
Increased Risk ◽  
Receptor Signaling Pathway ◽  
Platelet Reaction

Abstract Backgrounds: Remarkable interindividual variability in clopidogrel response is observed, genetic polymorphisms in P2RY12 and its signal pathway is supposed to affect clopidogrel response in CHD patients. Methods: 539 CHD patients treated with clopidogrel were recruited. The platelet reaction index (PRI) indicated by VASP-P level were detected in 12-24h after clopidogrel loading dose (LD) or within 5-7 days after initiation of maintain dose (MD) clopidogrel. A total of 13 SNPs in relevant genes were genotyped in sample A (239 CHD patients). The SNPs which have significant differences in PRI will be validated in another sample (sample B, 300 CHD patients). Results: CYP2C19*2 increased the risk of clopidogrel resistance significantly. When CYP2C19*2 and CYP2C19*3 were considered, CYP2C19 loss of function (LOF) alleles were associated with more obviously increased the risk of clopidogrel resistance; P2RY12 rs6809699 C>A polymorphism was also associated with increased risk of clopidogrel resistance (AA vs CC: P=0.0398). This difference still existed after stratification by CYP2C19 genotypes. It was also validated in sample B. The association was also still significant even in the case of stratification by CYP2C19 genotypes in all patients (sample A+B). Conclusion: Our data suggest that P2RY12 rs6809699 is associated with clopidogrel resistance in CHD patients. Meanwhile, the rs6809699 AA genotype can increase on-treatment platelet activity independent of CYP2C19 LOF polymorphisms.

Cost-effectiveness of Argatroban Versus Heparin Anticoagulation in Adult Extracorporeal Membrane Oxygenation Patients

2019 ◽  
pp. 001857871989009
Author(s):  
Angelina E. Cho ◽  
Kathleen Jerguson ◽  
Joy Peterson ◽  
Deepa V. Patel ◽  
Asif A. Saberi
Keyword(s):  
Cost Effectiveness ◽  
Extracorporeal Membrane Oxygenation ◽  
Average Cost ◽  
P Value ◽  
Bleeding Events ◽  
Membrane Oxygenation ◽  
Increased Risk ◽  
Heparin Anticoagulation ◽  
Ischemic Events ◽  
Ecmo Therapy

Purpose: The purpose of this study was to evaluate the cost effectiveness of argatroban compared to heparin during extracorporeal membrane oxygenation (ECMO) therapy. Methods: This was a retrospective study of patients who received argatroban or heparin infusions with ECMO therapy at a community hospital between January 1, 2017 and June 30, 2018. Adult patients who received heparin or argatroban for at least 48 hours while on venovenous (VV) or venoarterial (VA) ECMO were included. Patients with temporary mechanical circulatory assist devices were excluded. Each continuous course of anticoagulant exposure that met the inclusion criteria was evaluated. The primary endpoint was the total cost of anticoagulant therapy for heparin versus argatroban, including all administered study drugs, blood or factor products, and associated laboratory tests. Secondary endpoints included safety and efficacy of anticoagulation with each agent during ECMO. Documentation of bleeding events, circuit clotting, and ischemic events were noted. Partial thromboplastin time (PTT) values were evaluated for time to therapeutic range and percentage of therapeutic PTTs. Results: A total of 11 courses of argatroban and 24 courses of heparin anticoagulation were included in the study. The average cost per course of argatroban was less than the average cost per course of heparin ($7,091.98 vs $15,323.49, respectively; P value = 0.15). Furthermore, argatroban was not associated with an increased incidence of bleeding, thrombotic, or ischemic events. Conclusion: Argatroban may be more cost-effective during ECMO therapy in patients with low antithrombin III levels without increased risk of adverse events.

Incidence of cerebral ischemic events after discontinuation of clopidogrel in patients with intracranial aneurysms treated with stent-assisted techniques

2012 ◽  
Vol 117 (5) ◽  
pp. 929-933 ◽  
Author(s):  
James D. Rossen ◽  
Nohra Chalouhi ◽  
Shafik N. Wassef ◽  
Jacob Thomas ◽  
Taylor J. Abel ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Retrospective Review ◽  
Coil Embolization ◽  
Cerebral Aneurysms ◽  
Flow Diversion ◽  
Increased Risk ◽  
Cerebral Ischemic ◽  
Ischemic Events

Object The optimal antiplatelet medication protocol for prevention of thrombotic complications after stent-assisted coil embolization of cerebral aneurysms is unclear. Early cessation of antiplatelet agents may be associated with an increased risk of cerebral ischemic events. In this study, the authors assess the incidence of stroke or transient ischemic attack (TIA) following discontinuation of a 6-week course of clopidogrel in patients with cerebral aneurysms treated with stent-assisted techniques. Methods A retrospective review was conducted in all patients with cerebral aneurysms undergoing stent-assisted coil embolization or stent-in-stent flow diversion at the University of Iowa during a 24-month period. The antiplatelet protocol was 81 mg aspirin and 75 mg clopidogrel daily for 6 weeks, followed by 325 mg aspirin daily indefinitely. The incidence of stroke or TIA was determined by a retrospective review of medical records generated during a 3-month period following discontinuation of clopidogrel. Results A total of 154 patients underwent aneurysm treatment with stent techniques during this interval. Documentation of neurological follow-up 3 months after discontinuation of a 6-week clopidogrel treatment was available in 121 (78.6%) of 154 patients. Of these 121 patients, 114 were treated with stent-assisted coil embolization and 7 with stent-in-stent flow diversion. Six patients (5%) suffered an ischemic event after cessation of clopidogrel, with 2 events occurring within the first 2 weeks. Specifically, the rate of ischemic events was 5 (4.3%) of 114 in the “stent-coil” treatment group and 1 (14.3%) of 7 in the stent-in-stent group. Treatment had been performed in the setting of a subarachnoid hemorrhage in 1 patient. Atypical aneurysm features and technical factors predisposing to thrombotic events were found in all but one of these patients. Similarly, cardiovascular risk factors were present in 5 of the 6 patients in whom ischemic events developed after clopidogrel discontinuation. Conclusions Clopidogrel discontinuation is associated with a 5% risk of ischemic events in patients treated with stent techniques. Any stroke related to clopidogrel discontinuation is avoidable, and longer treatment is therefore clearly necessary. Patients with cardiovascular risk factors, high-risk aneurysm features, and those undergoing stent-in-stent flow diversion might benefit the most from longer clopidogrel therapy.

scholarly journals Implementation and management outcomes of pharmacogenetic CYP2C19 testing for clopidogrel therapy in clinical practice

2020 ◽  
Author(s):  
Stefan Russmann ◽  
Ali Rahmany ◽  
David Niedrig ◽  
Karl-Dietrich Hatz ◽  
Katja Ludin ◽  
...  
Keyword(s):  
Risk Factors ◽  
Clinical Practice ◽  
Successful Implementation ◽  
Control Analysis ◽  
Loss Of Function ◽  
Increased Risk ◽  
Clopidogrel Therapy ◽  
Management Recommendations ◽  
Case Control Analysis ◽  
Ischemic Events

Abstract Purpose The antiplatelet prodrug clopidogrel is bioactivated by the polymorphic enzyme CYP2C19. Prospective clinical studies demonstrated an association between CYP2C19 loss of function (LoF) variants and an increased risk of thrombotic events under clopidogrel, but pharmacogenetic (PGx) testing is not frequently implemented in clinical practice. We report our experience with PGx-guided clopidogrel therapy with particular regard to clinically relevant patient management changes. Methods We conducted an observational study analyzing patients that underwent PGx testing for clopidogrel therapy at two Swiss hospitals. Primary outcome was the proportion of patients with clinically relevant PGx-based management recommendations and their implementation. The association of recurrent ischemic events under clopidogrel with CYP2C19 LoF variants and other factors was explored in a multivariate case-control analysis. Results Among 56 patients undergoing PGx testing, 18 (32.1%) were classified as CYP2C19 intermediate or poor metabolizers. This resulted in 17 recommendations for a change of antiplatelet therapy, which were implemented in 12 patients (70.1%). In the remaining five patients, specific reasons for non-implementation could be identified. Recurrent ischemic events under clopidogrel were associated with LoF variants (OR 2.2, 95% CI 0.3–14.4) and several cardiovascular risk factors. Associations were not statistically significant in our small study, but plausible and in line with estimates from large prospective studies. Conclusion PGx-guided clopidogrel therapy can identify patients with an elevated risk of ischemic events and offer evidence-based alternative treatments. Successful implementation in clinical practice requires a personalized interdisciplinary service that evaluates indications and additional risk factors, provides specific recommendations, and proactively follows their implementation.

scholarly journals Blood Pressure Level and Variability During Long-Term Prasugrel or Clopidogrel Medication After Stroke

Stroke ◽  
2021 ◽  
Vol 52 (4) ◽  
pp. 1234-1243
Author(s):  
Kazunori Toyoda ◽  
Hiroshi Yamagami ◽  
Kazuo Kitagawa ◽  
Takanari Kitazono ◽  
Takehiko Nagao ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Ischemic Stroke ◽  
Hemorrhagic Stroke ◽  
Recurrent Stroke ◽  
Hazard Ratio ◽  
Observational Period ◽  
Bleeding Events ◽  
Increased Risk ◽  
Ischemic Events

Background and Purpose: High blood pressure increases bleeding risk during treatment with antithrombotic medication. The association between blood pressure levels and the risk of recurrent stroke during long-term secondary stroke prevention with thienopyridines (particularly prasugrel) has not been well studied. Methods: This was a post hoc analysis of the randomized, double-blind, multicenter PRASTRO-I trial (Comparison of Prasugrel and Clopidogrel in Japanese Patients With Ischemic Stroke-I). Patients with noncardioembolic stroke were randomly assigned (1:1) to receive prasugrel 3.75 mg/day or clopidogrel 75 mg/day for 96 to 104 weeks. Risks of any ischemic or hemorrhagic stroke, combined ischemic events, and combined bleeding events were determined based on the mean level and visit-to-visit variability, including successive variation, of systolic blood pressure (SBP) throughout the observational period. These risks were also compared between quartiles of mean SBP level and successive variation of SBP. Results: A total of 3747 patients (age 62.1±8.5 years, 797 women), with a median average SBP level during the observational period of 132.5 mm Hg, were studied. All the risks of any stroke (146 events; hazard ratio, 1.318 [95% CI, 1.094–1.583] per 10-mm Hg increase), ischemic stroke (133 events, 1.219 [1.010–1.466]), hemorrhagic stroke (13 events, 3.247 [1.660–6.296]), ischemic events (142 events, 1.219 [1.020–1.466]), and bleeding events (47 events, 1.629 [1.172–2.261]) correlated with increasing mean SBP overall. Similarly, an increased risk of these events correlated with increasing successive variation of SBP (hazard ratio, 3.078 [95% CI, 2.220–4.225] per 10-mm Hg increase; 3.051 [2.179–4.262]; 3.276 [1.172–9.092]; 2.865 [2.042–4.011]; 2.764 [1.524–5.016], respectively). Event rates did not differ between the clopidogrel and prasugrel groups within each quartile of SBP or successive variation of SBP. Conclusions: Both high mean SBP level and high visit-to-visit variability in SBP were significantly associated with the risk of recurrent stroke during long-term medication with either prasugrel or clopidogrel after stroke. Control of hypertension would be important regardless of the type of antiplatelet drugs. Registration: URL: https://www.clinicaltrials.jp ; Unique identifier: JapicCTI-111582.

Contrast-Enhanced Ultrasound: Identification of Neovascularization Permits Characterization of Vulnerable Carotid Plaques

2020 ◽  
Vol 36 (5) ◽  
pp. 471-477
Author(s):  
Jim Baun
Keyword(s):  
Significant Proportion ◽  
Contrast Enhanced Ultrasound ◽  
Atherosclerotic Vascular Disease ◽  
Ultrasound Evaluation ◽  
Contrast Enhanced ◽  
Increased Risk ◽  
Integral Role ◽  
Cerebral Ischemic ◽  
Ischemic Events

Objective: Carotid atherosclerotic vascular disease (ASVD) represents an ongoing health problem and is responsible for a significant proportion of all cerebral ischemic events (CIEs). Method: A review of the literature was performed on the application of contrast-enhanced ultrasound (CEUS) to enhance the diagnosis of ASVD and further avoid CIEs. Results: Cerebral ischemic events are those resulting from reduction or cessation of perfusion to localized regions of the brain made manifest by neurological, typically stroke-like, symptoms. Traditional triplex ultrasound evaluation is a reliable and widely established method of identifying carotid ASVD lesions and grading the accompanying degree of focal stenoses and their hemodynamic impact. While this information plays an integral role in determining management of patients with significant carotid ASVD, it is less useful in classifying individual lesions as “vulnerable” or not. Vulnerable lesions are those that, based on their histological and morphological features, predispose a patient to an increased risk of a CIE due to plaque or thrombus embolization. Conclusions: The addition of CEUS to carotid artery diagnostic studies offers new potential in identifying vulnerable plaques and predicting which patients will progress to sequelae associated with a cerebral ischemic event.

Omeprazole-clopidogrel interaction and neurovascular complications after flow-diverter device placement

2021 ◽  
pp. neurintsurg-2021-017397
Author(s):  
Joshua S Catapano ◽  
Visish M Srinivasan ◽  
Andre A Wakim ◽  
Jaclyn N Lundberg ◽  
Caleb Rutledge ◽  
...  
Keyword(s):  
Intracranial Aneurysms ◽  
Flow Diverter ◽  
Inhibitory Effect ◽  
Inclusion Criteria ◽  
Tertiary Institution ◽  
Increased Risk ◽  
Device Placement ◽  
Drug Eluting ◽  
The Mean ◽  
Ischemic Events

BackgroundOmeprazole is a common proton pump inhibitor that interferes with the hepatic activation of clopidogrel and potentially reduces its platelet-inhibitory effect. Omeprazole has been shown to increase P2Y12 levels and adverse cardiovascular outcomes in patients treated with drug-eluting stents. However, omeprazole use among patients treated with flow-diverting stents for intracranial aneurysms has not been evaluated.MethodsAll patients with placement of a flow-diverting device for treatment of an intracranial aneurysm at a tertiary institution from January 1, 2014, to December 31, 2018, were retrospectively analyzed. Inclusion criteria included documented clopidogrel administration, available P2Y12 levels, and thorough documentation of administration of other medications, including omeprazole.ResultsA total of 138 patients met the inclusion criteria. Sixteen patients (12%) were receiving omeprazole and clopidogrel at treatment. P2Y12 reactivity was significantly greater in the omeprazole cohort (mean P2Y12 level, 250 P2Y12 reaction units (PRU)) than in the control cohort (mean P2Y12 level, 112PRU) (P<0.001). Furthermore, a greater proportion of patients had a P2Y12 level >180 PRU in the omeprazole cohort (14 of 16 [88%] vs 24 of 122 [20%]; P<0.001; OR [95% CI], 29 [6–134]).ConclusionOmeprazole was associated with a significant increase in the mean P2Y12 reactivity level among patients with intracranial aneurysms treated with flow-diverting devices who received clopidogrel. However, receipt of omeprazole was not associated with an increased risk of ischemic events or stent stenosis. For neuroendovascular patients who are treated with a flow diverter while receiving clopidogrel, alternative gastrointestinal medication regimens should be considered.

Incomplete stent apposition in Enterprise stent–mediated coiling of aneurysms: persistence over time and risk of delayed ischemic events

2013 ◽  
Vol 118 (5) ◽  
pp. 1014-1022 ◽  
Author(s):  
Robert Heller ◽  
Daniel R. Calnan ◽  
Michael Lanfranchi ◽  
Neel Madan ◽  
Adel M. Malek
Keyword(s):  
Coil Embolization ◽  
Intracranial Aneurysms ◽  
Magnetic Resonance Images ◽  
Incomplete Stent Apposition ◽  
Multiplanar Reconstructions ◽  
Crescent Sign ◽  
Increased Risk ◽  
History Of ◽  
Ischemic Events

Object Incomplete stent apposition of the closed cell–design Enterprise stent following stent-mediated coil embolization of intracranial aneurysms has been associated with increased risk of periprocedural thromboembolic events. In this study, the authors seek to determine the natural history of incomplete stent apposition and evaluate the clinical implications of the phenomenon. Methods Since January 2009, all patients receiving Enterprise stents in the treatment of intracranial aneurysms at the authors' institution have undergone serial 3-T MRI with incomplete stent apposition identified by the crescent sign on multiplanar reconstructions of MR angiograms. Magnetic resonance images and MR angiograms obtained at 3, 9, and 18 months after stent-assisted coil embolization were analyzed along with admission and follow-up clinical medical records. These records were evaluated for any radiographic and clinical, transient or permanent ischemic neurological events. Results Fifty patients receiving Enterprise stents were eligible for inclusion and analysis in the study. Incomplete stent apposition was identified in postoperative imaging studies in 22 (44%) of 50 patients, with 19 (86%) of 22 crescent signs persisting and 3 (14%) of 22 crescent signs resolving on subsequent serial imaging. Delayed ischemic events occurred in 8 (16%) of 50 cases, and all cases involved patients with incomplete stent apposition. The events were transient ischemic attacks (TIAs) in 5 cases, asymptomatic radiographic strokes in 2 cases, and symptomatic strokes and TIAs in the final case. There were no delayed ischemic events in patients who did not have incomplete stent apposition. Only 1 of the delayed ischemic events (2%) was permanent and symptomatic. The postoperative presence of a crescent sign and persistence of the crescent sign were both significantly associated with delayed ischemic events (p < 0.001 and p = 0.002, respectively). Conclusions Incomplete stent apposition is a temporally persistent phenomenon, which resolves spontaneously in only a small minority of cases and appears to be a risk factor for delayed ischemic events. Although further follow-up is needed, these results suggest that longer duration of antiplatelet therapy and clinical follow-up may be warranted in cases of recognized incomplete stent apposition.

scholarly journals Gastro-Cardiology: A Novel Perspective for the Gastrocardiac Syndrome

2021 ◽  
Vol 8 ◽  
Author(s):  
Robin Hofmann ◽  
Magnus Bäck
Keyword(s):  
Helicobacter Pylori ◽  
Gastrointestinal Bleeding ◽  
Large Scale ◽  
Bleeding Events ◽  
Gastrointestinal Infections ◽  
Inflammatory Conditions ◽  
Increased Risk ◽  
Inflammatory Bowel ◽  
Ischemic Events ◽  
Cardiovascular Benefit

The gastrocardiac syndrome was coined originally at the beginning of the 19th century to describe an alleged gastric-cardiopathy with reflux heartburn mimicking cardiac chest pain. Today, a wider perspective of gastrocardiac syndrome has emerged. First, the cardiovascular risk factor chronic systemic inflammation may reflect gastroenterological inflammatory conditions, such as inflammatory bowel disease and gastrointestinal infections, in particular, chronic Helicobacter pylori infection. Furthermore, since contemporary treatment of cardiovascular disease commonly includes potent antithrombotic medications, the cardiovascular benefit in terms of a decrease in the incidence of recurrent ischemic events and death needs to be carefully balanced with an increased risk of gastrointestinal bleeding. Several strategies to target chronic gastrointestinal inflammation and to diagnose and treat Helicobacter pylori to reduce the risk of cardiovascular events and gastrointestinal bleeding are available but residual controversy remains and large-scale gastro-cardiology trials are needed to determine the optimal treatment approaches. In perspective, the centennial gastrocardiac syndrome is more relevant than ever in a contemporary gastroenterology and cardiology setting. A collaborative subspecialty, namely Gastro-cardiology, would introduce novel unique means to study, diagnose and treat gastrocardiac conditions with the aim to reduce the risk of cardiovascular and bleeding events to improve the prognosis for gastro-cardiology patients.

TLR1 and PRKAA1 Gene Polymorphisms in the Development of Atrophic Gastritis and Gastric Cancer

2018 ◽  
Vol 27 (4) ◽  
pp. 363-369 ◽  
Author(s):  
Gintare Dargiene ◽  
Greta Streleckiene ◽  
Jurgita Skieceviciene ◽  
Marcis Leja ◽  
Alexander Link ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Atrophic Gastritis ◽  
Genetic Polymorphisms ◽  
Association Studies ◽  
Control Group ◽  
Similar Distribution ◽  
Genome Wide Association Studies ◽  
Increased Risk ◽  
Infection Susceptibility ◽  
H Pylori

Background & Aims: Previous genome-wide association studies showed that genetic polymorphisms in toll-like receptor 1 (TLR1) and protein kinase AMP-activated alpha 1 catalytic subunit (PRKAA1) genes were associated with gastric cancer (GC) or increased Helicobacter pylori (H. pylori) infection susceptibility. The aim of this study was to evaluate the association between TLR1 and PRKAA1 genes polymorphisms and H.pylori infection, atrophic gastritis (AG) or GC in the European population.Methods: Single-nucleotide polymorphisms (SNPs) were analysed in 511 controls, 340 AG patients and 327 GC patients. TLR1 C>T (rs4833095) and PRKAA1 C>T (rs13361707) were genotyped by the real-time polymerase chain reaction. H. pylori status was determined by testing for anti-H. pylori IgG antibodies in the serum.Results: The study included 697 (59.2%) H. pylori positive and 481 (40.8%) H. pylori negative cases. We observed similar distribution of TLR1 and PRKAA1 alleles and genotypes in H. pylori positive and negative cases. TLR1 and PRKAA1 SNPs were not linked with the risk of AG. TC genotype of TLR1 gene was more prevalent in GC patients compared to the control group (29.7% and 22.3% respectively, p=0.002). Carriers of TC genotype had a higher risk of GC (aOR=1.89, 95% CI: 1.26–2.83, p=0.002). A similar association was observed in a dominant inheritance model for TLR1 gene SNP, where comparison of CC+TC vs. TT genotypes showed an increased risk of GC (aOR=1.86, 95% CI: 1.26–2.75, p=0.002). No association between genetic polymorphism in PRKAA1 gene and GC was observed.Conclusions: TLR1 rs4833095 SNP was associated with an increased risk of GC in a European population, while PRKAA1 rs13361707 genetic variant was not linked with GC. Both genetic polymorphisms were not associated with H. pylori infection susceptibility or the risk of AG.

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