A web resource for mining HLA associations with adverse drug reactions: HLA-ADR.

Human leukocyte antigens (HLA) are an important family of genes involved in the immune system. Their primary function is to allow the host immune system to be able to distinguish between self and non-self peptides-e.g. derived from invading pathogens. However, these genes have also been implicated in immune-mediated adverse drug reactions (ADRs), presenting a problem to patients, clinicians and pharmaceutical companies. We have previously developed the Allele Frequency Net Database (AFND) that captures the allelic and haplotype frequencies for these HLA genes across many healthy populations from around the world. Here, we report the development and release of the HLA-ADR database that captures data from publications where HLA alleles and haplotypes have been associated with ADRs (e.g. Stevens-Johnson Syndrome/toxic epidermal necrolysis and drug-induced liver injury). HLA-ADR was created by using data obtained through systematic review of the literature and semi-automated literature mining. The database also draws on data already present in AFND allowing users to compare and analyze allele frequencies in both ADR patients and healthy populations. The HLA-ADR database provides clinicians and researchers with a centralized resource from which to investigate immune-mediated ADRs.Database URL: http://www.allelefrequencies.net/hla-adr/

The rs1477196 SNP of the FTO Gene is Associated with Primary Knee Osteoarthritis in a Female Population from Northern Mexico

Background: Osteoarthritis is a frequent rheumatic disease. Some single-nucleotide polymorphisms of the gene associated with fat mass and obesity are associated with increased body mass index and knee osteoarthritis. Objective: The objective of this study was to analyze the association of single nucleotide polymorphism rs1477196 of the fat mass and obesity gene with primary knee osteoarthritis. Methods: This observational and cross-sectional study included 347 Mexican participants. We performed the genotypification analysis with TaqMan® probe C_2031262_10 for rs1477196 (Thermo Fisher Scientific). Multivariate analysis included covariables such as age, type 2 diabetes, obesity, and postmenopause. Results: Type 2 diabetes, obesity, and postmenopause were associated with primary knee osteoarthritis in female participants. We did not find an association between rs1477196 and obesity. In the codominant and dominant genetic models, rs1477196 was significantly associated with primary knee osteoarthritis only in the female group, including in the model adjusted by other covariables (odds ratio = 2.517; 1.035-6.123; p = 0.042 and odds ratio = 2.387; 1.054-5.407; p = 0.037, respectively). The interaction between rs1477196 and obesity was significantly associated with primary knee osteoarthritis in female participants (p = 0.039 and p = 0.043). Conclusions: Our findings suggest that the rs1477196 variant of the fat and obesity mass gene may be associated with the risk of primary knee osteoarthritis in women