PMID- 10896066
OWN - NLM
STAT- MEDLINE
DCOM- 20010222
LR  - 20190817
IS  - 0277-2116 (Print)
IS  - 0277-2116 (Linking)
VI  - 31
IP  - 1
DP  - 2000 Jul
TI  - Celiac disease and human leukocyte antigen genotype: accuracy of diagnosis in 
      self-diagnosed individuals, dosage effect, and sibling risk.
PG  - 22-7
AB  - BACKGROUND: Celiac disease is an autoimmune disorder of the small intestine 
      characterized by intolerance to gluten. Traditionally, diagnosis is made by 
      intestinal biopsy. Testing for immunoglobulin (Ig) A endomysial antibodies in the 
      serum also is used for diagnosis. Biopsy and serology revert to normal with 
      adherence to a gluten-free diet. Often, after an index case is diagnosed, 
      siblings with symptoms adhere to a gluten-free diet without biopsy or serologic 
      confirmation. More than 90% of patients with celiac disease have the human 
      leukocyte antigen (HLA) DQA1*0501-DQB1*0201 genotype. Non-HLA genes also have 
      been implicated. METHODS: One hundred ninety-five individuals with confirmed or 
      suspected celiac disease were identified in 73 families affected by the disease. 
      IgA endomysial antibody testing was performed for all symptomatic family members 
      who did not have biopsy-confirmed diagnoses. DNA samples were genotyped at D6S276 
      and the HLA class II loci DQA and DQB. RESULTS: At the time sampling was begun in 
      families, 88 of 177 (49.7%) individuals were self-diagnosed and adhering to a 
      gluten-free diet. Ninety percent (91/101) of confirmed cases (biopsy or serology) 
      had at least 1 copy of the DQA1*0501-DQB1*0201 genotype, whereas only 67% (46/69) 
      of cases self-diagnosed (adherence to gluten-free diet without confirmation) had 
      at least 1 copy. Of confirmed cases, 61% carried two copies of DQB*0201. It is 
      estimated that the HLA association and other unlinked genes contribute 
      approximately equally to the sibling risk of celiac disease. CONCLUSIONS: A 
      dosage effect of DQB1*0201 may be associated with an increased risk of celiac 
      disease. Self-diagnosis of celiac disease is as common as confirmed diagnosis in 
      families in the United States. Diagnosis of celiac disease on the basis of 
      clinical response to gluten restriction is inaccurate. With long-term adherence 
      to a gluten-free diet, serologic test results are likely to be negative. Based on 
      HLA genotype, approximately one third of self-diagnosed individuals are unlikely 
      to have celiac disease. However, it is not possible to determine which 
      individuals consuming a gluten-free diet have the disease. Therefore, before 
      starting a gluten-free diet, serologic screening and biopsy confirmation are 
      necessary.
FAU - Lewis, C
AU  - Lewis C
AD  - Division of Medical and Molecular Genetics, The Guy's, King's and St. Thomas's 
      School of Medicine, King's College, London, United Kingdom.
FAU - Book, L
AU  - Book L
FAU - Black, J
AU  - Black J
FAU - Sawitzke, A
AU  - Sawitzke A
FAU - Cannon-Albright, L
AU  - Cannon-Albright L
FAU - Zone, J
AU  - Zone J
FAU - Neuhausen, S
AU  - Neuhausen S
LA  - eng
GR  - R01-DK50678/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Pediatr Gastroenterol Nutr
JT  - Journal of pediatric gastroenterology and nutrition
JID - 8211545
RN  - 0 (HLA Antigens)
RN  - 0 (Immunoglobulin A)
RN  - 8002-80-0 (Glutens)
SB  - IM
CIN - J Pediatr Gastroenterol Nutr. 2002 Jan;34(1):91. PMID: 11753174
MH  - Biopsy
MH  - Celiac Disease/*diagnosis/genetics
MH  - Dermatitis Herpetiformis/*diagnosis/genetics
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Gene Dosage
MH  - Genotype
MH  - Glutens/adverse effects
MH  - HLA Antigens/*genetics
MH  - Haplotypes
MH  - Humans
MH  - Immunoglobulin A/analysis
MH  - Jejunum/pathology
MH  - Male
MH  - Nuclear Family
MH  - Prevalence
MH  - Risk Factors
MH  - Sensitivity and Specificity
EDAT- 2000/07/15 11:00
MHDA- 2001/03/03 10:01
CRDT- 2000/07/15 11:00
PHST- 2000/07/15 11:00 [pubmed]
PHST- 2001/03/03 10:01 [medline]
PHST- 2000/07/15 11:00 [entrez]
AID - 10.1097/00005176-200007000-00007 [doi]
PST - ppublish
SO  - J Pediatr Gastroenterol Nutr. 2000 Jul;31(1):22-7. doi: 
      10.1097/00005176-200007000-00007.