Dataset Information

Novel single nucleotide polymorphism markers for low dose aspirin-associated small bowel bleeding.

ABSTRACT:

Background

Aspirin-induced enteropathy is now increasingly being recognized although the pathogenesis of small intestinal damage induced by aspirin is not well understood and related risk factors have not been established.

Aim

To investigate pharmacogenomic profile of low dose aspirin (LDA)-induced small bowel bleeding.

Methods

Genome-wide analysis of single nucleotide polymorphisms (SNPs) was performed using the Affymetrix DMET™ Plus Premier Pack. Genotypes of candidate genes associated with small bowel bleeding were determined using TaqMan SNP Genotyping Assay kits and direct sequencing.

Results

In the validation study in overall 37 patients with small bowel bleeding and 400 controls, 4 of 27 identified SNPs: CYP4F11 (rs1060463) GG (p=0.003), CYP2D6 (rs28360521) GG (p=0.02), CYP24A1 (rs4809957) T allele (p=0.04), and GSTP1 (rs1695) G allele (p=0.04) were significantly more frequent in the small bowel bleeding group compared to the controls. After adjustment for significant factors, CYP2D6 (rs28360521) GG (OR 4.11, 95% CI. 1.62 -10.4) was associated with small bowel bleeding.

Conclusions

CYP4F11 and CYP2D6 SNPs may identify patients at increased risk for aspirin-induced small bowel bleeding.

SUBMITTER: Shiotani A

PROVIDER: S-EPMC3867469 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

Novel single nucleotide polymorphism markers for low dose aspirin-associated small bowel bleeding.

Shiotani Akiko A Murao Takahisa T Fujita Yoshihiko Y Fujimura Yoshinori Y Sakakibara Takashi T Nishio Kazuto K Haruma Ken K

PloS one 20131218 12

<h4>Background</h4>Aspirin-induced enteropathy is now increasingly being recognized although the pathogenesis of small intestinal damage induced by aspirin is not well understood and related risk factors have not been established.<h4>Aim</h4>To investigate pharmacogenomic profile of low dose aspirin (LDA)-induced small bowel bleeding.<h4>Methods</h4>Genome-wide analysis of single nucleotide polymorphisms (SNPs) was performed using the Affymetrix DMET™ Plus Premier Pack. Genotypes of candidate ge ...[more]

PMID: 24367646

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Project description:BackgroundLow-dose aspirin has proven effectiveness in secondary and primary prevention of cardiovascular events, but is also associated with an increased risk of major bleeding events. For primary prevention, this absolute risk must be carefully weighed against the benefits of aspirin; such assessments are currently limited by a lack of data from general populations.MethodsSystematic searches of Medline and Embase were conducted to identify observational studies published between 1946 and 4 March 2015 that reported the risks of gastrointestinal (GI) bleeding or intracranial hemorrhage (ICH) with long-term, low-dose aspirin (75-325 mg/day). Pooled estimates of the relative risk (RR) for bleeding events with aspirin versus non-use were calculated using random-effects models, based on reported estimates of RR (including odds ratios, hazard ratios, incidence rate ratios and standardized incidence ratios) in 39 articles.FindingsThe incidence of GI bleeding with low-dose aspirin was 0.48-3.64 cases per 1000 person-years, and the overall pooled estimate of the RR with low-dose aspirin was 1.4 (95% confidence interval [CI]: 1.2-1.7). For upper and lower GI bleeding, the RRs with low-dose aspirin were 2.3 (2.0-2.6) and 1.8 (1.1-3.0), respectively. Neither aspirin dose nor duration of use had consistent effects on RRs for upper GI bleeding. The estimated RR for ICH with low-dose aspirin was 1.4 (1.2-1.7) overall. Aspirin was associated with increased bleeding risks when combined with non-steroidal anti-inflammatory drugs, clopidogrel and selective serotonin reuptake inhibitors compared with monotherapy. By contrast, concomitant use of proton pump inhibitors decreased upper GI bleeding risks relative to aspirin monotherapy.ConclusionsThe risks of major bleeding with low-dose aspirin in real-world settings are of a similar magnitude to those reported in randomized trials. These data will help inform clinical judgements regarding the use of low-dose aspirin in prevention of cardiovascular events.

Project description:BackgroundOvert bleeding associated with low dose aspirin (LDA) is well-recognized, little attention is given to the possibility of association between LDA and occult bleeding, although this is known to occur in healthy volunteers. LDA is used increasingly in primary and secondary prevention of a number of medical conditions, many of which are common in older people, as is anemia. Anemia in older people is associated with adverse outcomes including disability, morbidity and mortality. The purpose of this study was to review the evidence that LDA might cause anemia without overt bleeding.MethodsAn extensive narrative review was carried out. Electronic searching (including database links) and reference lists of reports were used to identify studies reporting on use of aspirin ?325 mg/day and anemia or change in hemoglobin (Hb) without overt bleeding. Data were extracted from reports of trials, adverse drug reactions (ADRs) and prevalence studies of adults aged ?18 years, published since 1980.ResultsThere are few relevant data, with considerable heterogeneity among trial designs, duration, and patient characteristics in studies of LDA. In five randomised trials (n = 5879) in (mostly secondary) prevention, the majority of patients were men without peptic ulcer disease aged 50-70 years and no consistent association between LDA and change in Hb was found. In two smaller studies (n = 609) of primary prevention in healthy patients aged ?70 years, there was a small but statistically significant fall in Hb with LDA. Observational studies, and data from trials in which use of LDA was not a primary focus of the study, were inconclusive.ConclusionsIt is not clear whether there is an association between LDA and anemia in the absence of overt bleeding, but there may be an association between LDA and fall in Hb in (a subset of) older patients. The available evidence has significant limitations, which are discussed; studies including more older patients, and publication of individual patient data, would help clarify this important matter.

Dataset Information

Novel single nucleotide polymorphism markers for low dose aspirin-associated small bowel bleeding.

Background

Aim

Methods

Results

Conclusions

Publications

Novel single nucleotide polymorphism markers for low dose aspirin-associated small bowel bleeding.

Similar Datasets

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