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Objective Evidence is certainly mounting suggesting that a strong genetic RO4927350

Objective Evidence is certainly mounting suggesting that a strong genetic RO4927350 component underlies aspirin insensitivity. fail to reach RO4927350 this desired effect and instead they experience major adverse vascular events a phenomenon known as ‘aspirin insensitivity’ [2]. Since the discovery of this phenomenon to unravel the underlying mechanisms of aspirin insensitivity so far remains a daunting task. Evidence is mounting suggesting that a strong genetic component underlies aspirin insensitivity [3] [4]. Literature being abundant with candidate gene association studies [5]-[8] paves the way to determine how many genes and which genetic determinants are actually predisposing an individual to aspirin insensitivity [9]. However the resultant associations are often not reproducible likely due to the divergent ethnicity-specific genetic profiles the population stratification and cryptic relatedness the inadequate sample sizes and the lack of adjustment for confounders [10]-[12]. Mouse monoclonal to KRT13 To shed some light on this issue we sought to evaluate the association of four common polymorphisms (rs3842787: 50C→T rs20417: 765G→C rs201184269: 1565T→C rs1126643: 807C→T) with the risk of having aspirin insensitivity by conducting a meta-analysis of individual participant data from all qualified case-control studies. The four polymorphisms examined are mapped separately on four candidate genes: cyclooxygenase-1 (gene rs20417 and gene rs1126643 with aspirin insensitivity whereas no significance was found for gene rs3842787 and gene rs201184269 under both allelic and dominant models (Table 3). For instance risk estimates conferred by rs1126643-T allele reached as high as 2.37 (95% CI: 1.44-3.89; P?=?0.001) for the occurrence of aspirin insensitivity relative to the alternative allele and this estimation was more prominent under dominant model (OR?=?2.81; 95% CI: 1.54-5.13; P?=?0.001) despite marked between-study RO4927350 heterogeneity (P<0.01 for and genetic defects might increase the risk of having aspirin insensitivity especially for aspirin semi-resistance and in Chinese populations. However these significant associations were resulted from pooling a small number of studies with limited sample sizes and therefore our findings must be interpreted with caution. Aspirin insensitivity is a poorly characterized phenomenon in both clinical and laboratory contexts. Although the laboratory diagnosis of aspirin insensitivity cannot substitute clinical diagnosis there is every reason to believe that most if not all laboratory assays do reflect some rationale and degree of validity and sensitivity albeit variable of such insensitivity [31]. If not any real aspirin insensitive impact on clinical outcomes would be undetectable. A previous meta-analysis by the Antithrombotic Trialists' Collaboration documented that oral antiplatelet drugs in secondary prevention decreased the risk of a subsequent myocardial infarction by 25% and mortality by 20% among patients at high risk for cardiovascular events [32]. However even usage of such drugs also led to a residual rate of re-hospitalization among about 15% of patients with diagnosed ischemic heart disease [33]. One possible reason for this high readmission rate might be that there is a genetic component in the inherited susceptibility to aspirin insensitivity. As the number of candidate gene association studies is rapidly growing one practical way to unveil the genetic basis of aspirin insensitivity is to systematically pool available data to obtain robust replicable findings. In this study we evaluated the association of four common polymorphisms from four logical candidate genes (and genetic polymorphisms in susceptibility to aspirin insensitivity; however after stratifying studies by ethnicity the risk estimates were strongly reinforced in populations of Chinese origin relative to that of Caucasian origin. One possible explanation for this divergence is genetic heterogeneity across races and ethnicities. For example the average frequency of gene rs1126643-T allele was 40.77% in Caucasian patients with aspirin insensitivity RO4927350 but was as exceedingly high as 58.58% in Chinese patients. It is not uncommon to encounter genetic heterogeneity in any disease identification strategy. This ethnicity-specific effect suggests that different genetic backgrounds may account for this discrepancy or that different populations may have different linkage.