As patients with NSAIDs-exacerbated chronic urticaria showed a similar profile, this hypothesis was also extended to MNSAID-UA. Nevertheless, the inhibition of COX-1 cannot explain either the high basal concentration of LTE4 in urine or the overproduction of PGD2 during bronchoconstriction in AERD. Moreover, a recent study found no differences in the levels of PGE2 and LTs between AERD and asthmatic patients with good tolerance to aspirin. Apart from the characterization of intermediate phenotypes, considerable efforts have been taken to disentangle the genetics of CRI, mainly through the candidate gene approach. Most studies have considered AERD or CU, however MNSAID-UA is now being analyzed in more detail. Although only two genome-wide association studies have been conducted in CRI, both focusing on AERD, this information can be of utility to analyze the underlying mechanisms in MNSAID-UA. The more recent of the two studies suggests a potential role for the HLA system, but the presentation of the parental drug or their metabolites are not thought to be involved in this pathology. Importantly, one of them Z-VAD-FMK 187389-52-2 proposed the CEP68 gene, encoding the centrosomal protein of 68 kDa, as a susceptibility locus for AERD. In this study we aimed to analyze the potential role of common genetic variants in CEP68 gene in the predisposition to MNSAID-UA, the most frequent clinical entity in HRs to drugs. We studied a well-characterized group of Spanish patients with MNSAID-UA, defined as skin reactions in the absence of airway exacerbations or underlying chronic urticaria. We also extended this analysis to two small groups of patients with airway exacerbations or with blended reactions. To our knowledge, this is the first time that genes different from those related to AA metabolism or to inflammatory mediators have been analyzed in the context of MNSAID-UA susceptibility. To date, the study of the genetic basis of NSAIDs hypersensitivity has focused mainly in AERD and CU, and followed the candidate gene approach considering genes related with the AA pathway. Furthermore, the two GWAS in HRs published to date have been performed using a limited number of samples and only including patients with aspirin-induced asthma. One of such studies associated the non-synonymous polymorphism rs7572857 in CEP68 gene with changes in forced expiratory volume after aspirin administration, and proposed CEP68 as a susceptibility gene for aspirin intolerance in asthmatics. Here we evaluated the potential role of common genetic variants in this gene with MNSAID-UA susceptibility in a well-characterized group of patients. For this, we efficiently captured common variation of the gene by genotyping a set of 6 tagSNPs, including rs7572857, and boosted the study power by testing the association of 10 times more variants of this locus than in previous studies, by means of genotype imputation. In the GWAS identifying CEP68 as a key locus for HRs susceptibility associated with AERD, the association of rs7572857 was prominent and put forward as the potential causal variant affecting the polarity of the encoded protein and/or its function.