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A case-control study of the association between polymorphisms of the endothelial nitric oxide synthase and glycoprotein IIIa genes and upper gastrointestinal bleeding in users of low-dose aspirin.
Clin Ther. 2008 Jan; 30(1):121-30.CT

Abstract

BACKGROUND

Previous studies have reported a potential genetic predisposition to NSAID-related upper gastrointestinal (GI) bleeding.

OBJECTIVE

This study evaluated whether there was an association between 2 polymorphisms--the platelet glycoprotein (GP) IIIa PlA1/A2 polymorphism and the 27-bp VNTR (variable number of tandem repeats) polymorphism in intron 4 of the endothelial nitric oxide synthase (eNOS) gene--and a risk for nonvariceal upper GI bleeding in Spanish patients taking low-dose aspirin for secondary prophylaxis of vascular occlusive diseases.

METHODS

Genotyping for the 2 polymorphisms was performed in patients hospitalized for upper GI bleeding associated with the use of low-dose aspirin between September 1998 and October 2000, and race-, age-, and sex-matched controls who were taking low-dose aspirin but had no history of upper GI bleeding. To ascertain allele frequencies in a healthy population, genotyping was also performed in an unmatched group of blood donors.

RESULTS

The study included 88 white patients (65 men, 23 women; mean age, 67.5 years) with an episode of upper GI bleeding, 108 matched controls with no history of upper GI bleeding (79 men, 29 women; mean age, 65.9 years), and 158 blood-donor controls (109 men, 49 women; mean age, 53.4 years). No significant differences were found between cases and controls in terms of genotype, carriage, or allele frequency of the GPIIIa PlA1/A2 polymorphism. However, after adjustment for confounding variables, logistic regression analysis indicated an association between carriage of the eNOS "a" allele and a reduced risk of upper GI bleeding (odds ratio [OR] 0.39; 95 CI, 0.18-0.85; P 0.018). In this model, treatment with nitrovasodilators (OR 0.28; 95 CI, 0.12-0.66; P 0.004) and use of antisecretory drugs (OR 0.15; 95 CI, 0.05-0.47; P 0.001) were also identified as protective factors. Helicobacter pylori infection (OR 3.07; 95 CI, 1.23-7.70; P 0.017), alcohol consumption (OR 5.04; 95 CI, 1.86-13.70; P 0.001), and a history of peptic ulcer (OR 13.41; 95 CI, 3.78-47.64; P 0.001) were identified as risk factors for upper GI bleeding.

CONCLUSION

In this small, selected population of individuals taking low-dose aspirin for secondary prevention, carriage of the "a" allele of the eNOS gene was associated with a decreased risk for upper GI bleeding.

Authors+Show Affiliations

Instituto Aragonés de Ciencias de la Salud, Zaragoza, Spain. epiazor@unizar.esNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18343248

Citation

Piazuelo, Elena, et al. "A Case-control Study of the Association Between Polymorphisms of the Endothelial Nitric Oxide Synthase and Glycoprotein IIIa Genes and Upper Gastrointestinal Bleeding in Users of Low-dose Aspirin." Clinical Therapeutics, vol. 30, no. 1, 2008, pp. 121-30.
Piazuelo E, Fuentes J, García-González MA, et al. A case-control study of the association between polymorphisms of the endothelial nitric oxide synthase and glycoprotein IIIa genes and upper gastrointestinal bleeding in users of low-dose aspirin. Clin Ther. 2008;30(1):121-30.
Piazuelo, E., Fuentes, J., García-González, M. A., Jiménez, P., & Lanas, A. (2008). A case-control study of the association between polymorphisms of the endothelial nitric oxide synthase and glycoprotein IIIa genes and upper gastrointestinal bleeding in users of low-dose aspirin. Clinical Therapeutics, 30(1), 121-30. https://doi.org/10.1016/j.clinthera.2008.01.020
Piazuelo E, et al. A Case-control Study of the Association Between Polymorphisms of the Endothelial Nitric Oxide Synthase and Glycoprotein IIIa Genes and Upper Gastrointestinal Bleeding in Users of Low-dose Aspirin. Clin Ther. 2008;30(1):121-30. PubMed PMID: 18343248.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A case-control study of the association between polymorphisms of the endothelial nitric oxide synthase and glycoprotein IIIa genes and upper gastrointestinal bleeding in users of low-dose aspirin. AU - Piazuelo,Elena, AU - Fuentes,Javier, AU - García-González,María Asunción, AU - Jiménez,Pilar, AU - Lanas,Angel, PY - 2007/10/20/accepted PY - 2008/3/18/pubmed PY - 2009/9/16/medline PY - 2008/3/18/entrez SP - 121 EP - 30 JF - Clinical therapeutics JO - Clin Ther VL - 30 IS - 1 N2 - BACKGROUND: Previous studies have reported a potential genetic predisposition to NSAID-related upper gastrointestinal (GI) bleeding. OBJECTIVE: This study evaluated whether there was an association between 2 polymorphisms--the platelet glycoprotein (GP) IIIa PlA1/A2 polymorphism and the 27-bp VNTR (variable number of tandem repeats) polymorphism in intron 4 of the endothelial nitric oxide synthase (eNOS) gene--and a risk for nonvariceal upper GI bleeding in Spanish patients taking low-dose aspirin for secondary prophylaxis of vascular occlusive diseases. METHODS: Genotyping for the 2 polymorphisms was performed in patients hospitalized for upper GI bleeding associated with the use of low-dose aspirin between September 1998 and October 2000, and race-, age-, and sex-matched controls who were taking low-dose aspirin but had no history of upper GI bleeding. To ascertain allele frequencies in a healthy population, genotyping was also performed in an unmatched group of blood donors. RESULTS: The study included 88 white patients (65 men, 23 women; mean age, 67.5 years) with an episode of upper GI bleeding, 108 matched controls with no history of upper GI bleeding (79 men, 29 women; mean age, 65.9 years), and 158 blood-donor controls (109 men, 49 women; mean age, 53.4 years). No significant differences were found between cases and controls in terms of genotype, carriage, or allele frequency of the GPIIIa PlA1/A2 polymorphism. However, after adjustment for confounding variables, logistic regression analysis indicated an association between carriage of the eNOS "a" allele and a reduced risk of upper GI bleeding (odds ratio [OR] 0.39; 95 CI, 0.18-0.85; P 0.018). In this model, treatment with nitrovasodilators (OR 0.28; 95 CI, 0.12-0.66; P 0.004) and use of antisecretory drugs (OR 0.15; 95 CI, 0.05-0.47; P 0.001) were also identified as protective factors. Helicobacter pylori infection (OR 3.07; 95 CI, 1.23-7.70; P 0.017), alcohol consumption (OR 5.04; 95 CI, 1.86-13.70; P 0.001), and a history of peptic ulcer (OR 13.41; 95 CI, 3.78-47.64; P 0.001) were identified as risk factors for upper GI bleeding. CONCLUSION: In this small, selected population of individuals taking low-dose aspirin for secondary prevention, carriage of the "a" allele of the eNOS gene was associated with a decreased risk for upper GI bleeding. SN - 1879-114X UR - https://www.unboundmedicine.com/medline/citation/18343248/A_case_control_study_of_the_association_between_polymorphisms_of_the_endothelial_nitric_oxide_synthase_and_glycoprotein_IIIa_genes_and_upper_gastrointestinal_bleeding_in_users_of_low_dose_aspirin_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0149-2918(08)00068-4 DB - PRIME DP - Unbound Medicine ER -