title: Increased prevalence of celiac disease without gastrointestinal symptoms in adults MICA 5.1 homozygous subjects from the Campania area.
abstract: OBJECTIVE
  Polymorphisms in the major histocompatibility complex class I chain-related gene A may influence its binding to the Natural Killer Cell Receptor G2D (NKG2D). We looked for polymorphisms in major histocompatibility complex class I chain-related gene A exon 5 and in Human Leukocyte Antigen (HLA)-DQ/DR in adult coeliac disease patients to determine whether they affected coeliac disease phenotypes.
  
  
  METHODS
  Adult coeliac disease patients with (n=98) and without (n=93) gastrointestinal symptoms (gastrointestinal symptoms+/gastrointestinal symptoms-) and 108 control subjects from Campania (Italy) were characterized by Polymerase Chain Reaction (PCR) sequence specific oligonucleotide followed by PCR sequence specific primer assays for HLA DQ/DR, and by PCR followed by capillary electrophoresis for major histocompatibility complex class I chain-related gene A exon 5 polymorphisms. Immunoglobulin A (IgA) anti-transglutaminase antibodies were also evaluated by immunosorbent assay.
  
  
  RESULTS
  Five different major histocompatibility complex class I chain-related gene A alleles were detected in both coeliac disease patients and control subjects. The major histocompatibility complex class I chain-related gene A 5.1 allele occurred more frequently in patients than in controls (p<0.05), and the major histocompatibility complex class I chain-related gene A 5.1/5.1 homozygous genotype increased the risk of gastrointestinal symptoms- coeliac disease (OR=2.79, 95% CI 1.15-6.79). Gastrointestinal symptoms- coeliac disease patients bearing major histocompatibility complex class I chain-related gene A 5.1/5.1 alleles showed lower anti-transglutaminase levels (18U/L) than the gastrointestinal symptoms+ coeliac disease patients (35U/L). HLA-DQ2/DQ8 genotypes did not differ between gastrointestinal symptoms+ and gastrointestinal symptoms- coeliac disease, although DQ8 tended to be more frequent in gastrointestinal symptoms- coeliac disease (11.7%) than in gastrointestinal symptoms+ coeliac disease (6%).
  
  
  CONCLUSIONS
  Our study shows that a double dose of the major histocompatibility complex class I chain-related gene A 5.1 allele could predispose to the onset of gastrointestinal symptoms- coeliac disease. We can hypothesize that a lower level of immunological involvement in gastrointestinal symptoms- coeliac disease patients is associated with absence of gastrointestinal symptoms. This test could represent a second step in the genetic typing of high-risk subjects such as first-degree relatives of coeliac disease patients positive for the DQ2/DQ8 molecule.
authors.affiliation: Department of Biochemistry and Medical Biotechnology, Federico II University Medical School, Naples, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Tinto
authors.forename: C
authors.initials: C
authors.lastname: Ciacci
authors.forename: G
authors.initials: G
authors.lastname: Calcagno
authors.forename: D
authors.initials: D
authors.lastname: Gennarelli
authors.forename: A
authors.initials: A
authors.lastname: Spampanato
authors.forename: E
authors.initials: E
authors.lastname: Farinaro
authors.forename: R
authors.initials: R
authors.lastname: Tortora
authors.forename: L
authors.initials: L
authors.lastname: Sacchetti
mesh_terms: D000328:Adult; D002446:Celiac Disease / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D011110:Polymorphism, Genetic; D015995:Prevalence
chemical_list: D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A