RESUMO
Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gut. Genetic association studies have identified the highly variable human leukocyte antigen (HLA) region as the strongest susceptibility locus for IBD and specifically DRB1*01:03 as a determining factor for ulcerative colitis (UC). However, for most of the association signal such as delineation could not be made because of tight structures of linkage disequilibrium within the HLA. The aim of this study was therefore to further characterize the HLA signal using a transethnic approach. We performed a comprehensive fine mapping of single HLA alleles in UC in a cohort of 9272 individuals with African American, East Asian, Puerto Rican, Indian and Iranian descent and 40 691 previously analyzed Caucasians, additionally analyzing whole HLA haplotypes. We computationally characterized the binding of associated HLA alleles to human self-peptides and analyzed the physicochemical properties of the HLA proteins and predicted self-peptidomes. Highlighting alleles of the HLA-DRB1*15 group and their correlated HLA-DQ-DR haplotypes, we not only identified consistent associations (regarding effects directions/magnitudes) across different ethnicities but also identified population-specific signals (regarding differences in allele frequencies). We observed that DRB1*01:03 is mostly present in individuals of Western European descent and hardly present in non-Caucasian individuals. We found peptides predicted to bind to risk HLA alleles to be rich in positively charged amino acids. We conclude that the HLA plays an important role for UC susceptibility across different ethnicities. This research further implicates specific features of peptides that are predicted to bind risk and protective HLA proteins.
Assuntos
Colite Ulcerativa/genética , Etnicidade/genética , Predisposição Genética para Doença , Antígenos HLA/genética , Antígenos HLA-DQ/genética , Cadeias HLA-DRB1/genética , Peptídeos/genética , Alelos , Estudos de Coortes , Frequência do Gene , Estudos de Associação Genética , Genótipo , Haplótipos , Humanos , Desequilíbrio de Ligação , Polimorfismo de Nucleotídeo Único , Ligação ProteicaRESUMO
BACKGROUND: Food adulteration including adulteration of edible oils may cause serious health problems. One of the most common edible adulterants is argemone oil. An outbreak of epidemic dropsy occurred in Addis Ababa during May-June, 2008. One hundred and eighty two cases were recorded with twelve confirmed deaths. Dietary history of the cases revealed that vegetable oils were the usual cooking medium. OBJECTIVE: The aim of the study was hence to investigate the causes of this outbreak. METHODS: Contaminant identification was done using standard chemical tests, complemented with TLC. Toxicity study was done using Swiss albino mice feed with contaminated and non contaminated standard diet for 30 days. RESULTS: Laboratory investigation of the edible oils has indicated that 47 of the 280 edible oils analyzed were adulterated with argemone oil. About 81% of the edible oil samples collected from Lideta sub-city were adulterated with argemone oil. Toxicological investigation of the adulterated oils also indicated typical features of argemone alkaloid poisoning in mice. CONCLUSION: Results of both laboratory analysis and toxicological studies confirmed consumption of edible oils adulterated with argemone oil as the cause of epidemic dropsy in Addis Ababa.