letter to tHe eDitor

Bhat M, Lu Y, Marcil V, et al. Tumour necrosis factor-alpha polymorphism increases the risk for nonvariceal upper gastrointestinal bleeding in patients taking proton pump inhibitors. Can J Gastroenterol Hepatol 2014;28(9):488. To the Editor: Nonvariceal upper gastrointestinal bleeding (NVUGIB) is associated with significant morbidity, affecting 50 to 150 per 100,000 adults annually (1). Patients with NVUGIB may present with melena, hematochezia or coffee-ground emesis, often accompanied by a decrease in hemoglobin levels and even hemodynamic instability. Nonsteroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori infection are the principal risk factors for NVUGIB, accounting for >95% of cases. Taking proton pump inhibitors (PPIs) is a known protective factor against NVUGIB. There has recently been growing interest in a possible genetic predisposition to NVUGIB, with investigation of single nucleotide polymorphisms (SNPs) associated with bleeding events. Of particular interest have been mutations in proinflammatory genes or genes that regulate NSAID/PPI metabolism, which may contribute to excessive inflammation and ulceration in the context of H pylori infection and NSAID use. A recent pharmacogenomic study The above literature describing a genetic predisposition for bleeding events applies principally to East Asian patient populations. Therefore, we decided to study whether such genetic associations could be elicited in the Canadian context. We performed a pilot study to assess the association of SNPs involved in NSAID metabolism (CYP2C9) and inflammatory response (TNF-α) with NVUGIB events. Patients who were part of the REASON-II NVUGIB study population at the McGill University Health Centre (Montreal, Quebec) were recruited (5). Study controls were asymptomatic patients undergoing screening colonoscopy, and excluded if there was any history of NVUGIB. DNA extracted from serum was genotyped for SNPs in the proinflammatory TNF-α (rs1799724, rs1800630, rs1799964) and NSAID-metabolizing CYP2C9 genes (rs1799853, rs1057910). Using STATA version 10, we assessed for any association between SNPs and NVUGIB events using logistic regression analysis and stratifying according to H pylori status, NSAID and PPI use. Our study included 23 patients and 46 controls of comparable age and sex, with NSAID (26.1% versus 6.7%) and PPI use (21.7% versus 13.0%) being more prevalent among patients. The TNFα1031C SNP, a proinflammatory cytokine polymorphism, was more common among patients with NVUGIB (OR 2.2 [95% CI 0.9 to 5.1]; P=0.084), particularly among those using PPIs (OR 20.0 [95% CI 0.9 to 429.9]; P=0.056) or not taking NSAIDs (OR 3.2 [95% CI 1.1 to 9.0]; P=0.027) at the time of the bleeding event. There was a trend in association of the TNF-α863A SNP with NVUGIB in patients not taking NSAIDs (OR 2.7 [95% CI 0.9 to 8.6]; P=0.071). We did not detect an association between CYP2C9 polymorphisms and NVUGIB, a result similar to that obtained in the study by Musumba et al (2). In conclusion, our pilot study demonstrates that TNF-α1031C SNP confers a risk for NVUGIB events among patients taking PPIs, a finding compatible with previous studies showing increased risk for peptic ulceration with this particular SNP (3

Recommendations for the appropriate use of anti-inflammatory drugs in the era of the coxibs: Defining the role of gastroprotective agents

Treatment with anti-inflammatory drugs and the analgesic efficacy of conventional nonsteroidal anti-inflammatory drugs (NSAIDs) are compromised by a two-to fourfold increased risk of gastrointestinal complications. This increased risk has resulted in an increasing use of the new selective cyclooxygenase-2 inhibitors or coxibs, which, in clinical trials and outcomes studies, reduced gastrointestinal adverse events by 50% to 65% compared with conventional NSAIDs. However, the coxibs are not available to all patients who need them, and NSAIDs are still widely used. Moreover, treatment with a coxib cannot heal preexisting gastrointestinal lesions, and cotherapy with an antisecretory drug or mucosal protective agent may be required. This paper addresses the management of patients with risk factors for gastrointestinal complications who are taking NSAIDs and makes recommendations for the appropriate use of 'gastroproteccontinued on next pag