Abstract
Bleeding in non-steroidal anti-inflammatory drug (NSAID) users limited their prescription. This first multicenter full case–control study (325 cases and 744 controls), explored the association of e-NOS intron 4 variable number tandem repeat (VNTR) polymorphism with upper gastrointestinal hemorrhage (UGIH) in NSAID exposed and unexposed populations and assessed any interaction between this polymorphism and NSAIDs. NSAID users carrying e-NOS intron 4 wild type genotype or VNTR polymorphism have higher odds of UGIH than those unexposed to NSAIDs [Odds Ratio (OR): 6.62 (95% Confidence Interval (CI): 4.24, 10.36) and OR: 5.41 (95% CI 2.62, 11.51), respectively], with no effect modification from VNTR polymorphism-NSAIDs interaction [Relative Excess Risk due to Interaction (RERI): −1.35 (95% CI −5.73, 3.03); Synergism Index (S): 0.77 (95% CI 0.31, 1.94)]. Similar findings were obtained for aspirin exposure. Non-aspirin NSAID users who carry e-NOS intron 4 VNTR polymorphism have lower odds of UGIH [OR: 4.02 (95% CI 1.85, 8.75) than those users with wild type genotype [OR: 6.52 (95% CI 4.09, 10.38)]; though the interaction estimates are not statistically significant [RERI: −2.68 (95% CI −6.67, 1.31); S: 0.53 (95% CI 0.18, 1.55)]. This exploratory study suggests that the odds of UGIH in NSAID or aspirin users does not modify according to patient´s e-NOS intron 4 genotype.
Highlights
Mainly gastrointestinal bleeding, have limited the application of non-steroidal anti-inflammatory drug (NSAID) and aspirin in primary prevention[11,12,13]
In a recent study on the effect of polymorphisms on aspirin-related upper gastrointestinal hemorrhage (UGIH), we suggested that aspirin users who carry the inherited allele of rs1799983 polymorphism of NOS3 gene have lower odds of UGIH21
In this multicentre case–control study, we conducted an exploratory analysis of the effect of eNOS intron 4 variable number of tandem repeat (VNTR) polymorphism on UGIH in users and non-users of NSAIDs
Summary
Mainly gastrointestinal bleeding, have limited the application of NSAIDs and aspirin in primary prevention[11,12,13]. Circulating NO is mainly produced by endothelial NO synthase (e-NOS) and plays a fundamental role in protecting the gastric mucosa, repairing gastric damage induced by NSAIDs and aspirin, regulating blood flow, fostering angiogenesis, preventing thrombosis, cardiac or vascular contractility, controlling cardiovascular tissue remodeling, and inhibiting platelet aggregation[24,25,26,27]. The lack of data about individuals unexposed to aspirin in that s tudy[32], makes it impossible to determine whether the reported reduced risk of UGIH is due to a protective effect of 4a e-NOS allele itself or generated from a modification of effect from an interaction between this genetic variation and aspirin, in which case, further investigation is needed
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