ABSTRACT
Genetic polymorphisms in the endoplasmic reticulum aminopeptidase (ERAP)1 and ERAP2 genes have been associated with several autoimmune diseases (AIDs) at a genome-wide significance level. In this study, we performed a cis expression quantitative trait locus (eQTL) screen to investigate whether seven fine-mapped AID single-nucleotide polymorphisms (SNPs) in the ERAP-region influence the gene-expression levels of ERAP1 and ERAP2 in thymus. After quality control, we identified six significant eQTLs. We further assessed the peak eQTL signals, and both genes showed highly significant and independent thymic eQTL signals (P=2.16 × 10-15 and P=8.22 × 10-23, respectively). Interestingly, the peak eQTL signal overlapped with the AID risk loci in ERAP2 (r2>0.94), but were distinct in ERAP1 (r2<0.4). Finally, among the SNPs showing the most significant eQTL associations with ERAP2 (P<3.4 × 10-20), six were located within transcription factor motifs in an enhancer region in thymus. Our study therefore reveals the fine-mapped AID risk variants that act as eQTLs with ERAP2 in thymus, and highlights the potential causal regulatory variants.
Subject(s)
Aminopeptidases/genetics , Autoimmune Diseases/genetics , Thymus Gland/metabolism , Child , Child, Preschool , Female , Gene Expression , Haplotypes , Humans , Infant , Linkage Disequilibrium , Male , Minor Histocompatibility Antigens/genetics , Organ Specificity , Polymorphism, Single Nucleotide , Quantitative Trait Loci , Risk FactorsABSTRACT
OBJECTIVE: To determine if faecal calprotectin concentrations vary with different entities of functional gastrointestinal disorders (FGID) in children. METHODS: Children (4-15 years) who were consecutively referred by general practitioners to four general paediatric outpatient clinics for the evaluation of recurrent abdominal pain were assessed according to a research protocol which included clinical examination, a minimum set of blood, urine and stool tests, and clinical reassessment after 6-9 months. The diagnoses of FGID were based on the parent version of the Questionnaire on Pediatric Gastrointestinal Symptoms-Rome III. RESULTS: Of the 152 patients included, 142 children were diagnosed with FGID. Of these, 126 (89%) provided a stool specimen for quantification of calprotectin. The median calprotectin concentrations were at or lower than 16 mg/kg which was at the lower detection limit and there were no differences between the FGID subgroups. Nine children (7%) had slightly raised values. CONCLUSION: The faecal calprotectin concentration is within normal limits in FGID and does not vary with different FGID entities suggesting that bowel inflammation is not a significant part of the pathogenesis in FGID.