PMID- 14517787
OWN - NLM
STAT- MEDLINE
DCOM- 20031030
LR  - 20190707
IS  - 0016-5085 (Print)
IS  - 0016-5085 (Linking)
VI  - 125
IP  - 4
DP  - 2003 Oct
TI  - A major non-HLA locus in celiac disease maps to chromosome 19.
PG  - 1032-41
AB  - BACKGROUND AND AIMS: The pathogenesis of celiac disease is still unknown despite 
      its well-known association with human leukocyte antigen (HLA)-DQ2 and DQ8. It is 
      clear that non-HLA genes contribute to celiac disease development as well, but 
      none of the previous genome-wide screens in celiac disease have resulted in 
      identification of these genes. METHODS: We, therefore, performed a 2-stage, 
      genome-wide screen in 101 affected sibpairs from 82 Dutch families who met strict 
      diagnostic criteria. The small intestinal biopsy samples, on which the original 
      celiac disease diagnoses had been based, showed a Marsh III lesion in all 
      patients on reevaluation by 1 pathologist. For association analysis of markers in 
      regions linked to celiac disease, 216 independent MIII patients and 216 age- and 
      sex-matched controls were available. RESULTS: As expected, highly significant 
      linkage to the HLA-region was detected (multipoint maximum lod score [MMLS] = 
      8.14). More importantly, significant linkage was also present at 19p13.1 (MMLS = 
      4.31), with the peak at marker D19S899. Moreover, this marker was also 
      significantly associated with celiac disease in the case-control study (corrected 
      P = 0.016). Furthermore, we identified suggestive linkage to 6q21-22, which is 
      approximately 70 cM downstream from the HLA region (MMLS = 3.10). CONCLUSIONS: 
      Significant linkage of celiac disease to chromosome region 19p13.1 was detected 
      in our genome-wide screen. These results were confirmed by the association of 
      D19S899 to celiac disease in an independent case-control cohort. Furthermore, we 
      identified a possible second celiac disease locus on chromosome region 6q21-22.
FAU - Van Belzen, Martine J
AU  - Van Belzen MJ
AD  - Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The 
      Netherlands.
FAU - Meijer, Jos W R
AU  - Meijer JW
FAU - Sandkuijl, Lodewijk A
AU  - Sandkuijl LA
FAU - Bardoel, Alfons F J
AU  - Bardoel AF
FAU - Mulder, Chris J J
AU  - Mulder CJ
FAU - Pearson, Peter L
AU  - Pearson PL
FAU - Houwen, Roderick H J
AU  - Houwen RH
FAU - Wijmenga, Cisca
AU  - Wijmenga C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Gastroenterology
JT  - Gastroenterology
JID - 0374630
RN  - 0 (Genetic Markers)
RN  - 0 (HLA-DQ Antigens)
SB  - IM
CIN - Gastroenterology. 2004 Apr;126(4):1216-7; author reply 1217. PMID: 15057768
MH  - Adult
MH  - Age of Onset
MH  - Case-Control Studies
MH  - Celiac Disease/*genetics
MH  - Child
MH  - Chromosomes, Human, Pair 1
MH  - *Chromosomes, Human, Pair 19
MH  - Chromosomes, Human, Pair 20
MH  - Chromosomes, Human, Pair 5
MH  - Chromosomes, Human, Pair 6
MH  - Chromosomes, Human, Pair 8
MH  - Cohort Studies
MH  - Family Health
MH  - Female
MH  - Genetic Markers
MH  - Genome, Human
MH  - HLA-DQ Antigens/genetics
MH  - Histocompatibility Testing
MH  - Humans
MH  - *Lod Score
MH  - Male
MH  - Netherlands
EDAT- 2003/10/01 05:00
MHDA- 2003/10/31 05:00
CRDT- 2003/10/01 05:00
PHST- 2003/10/01 05:00 [pubmed]
PHST- 2003/10/31 05:00 [medline]
PHST- 2003/10/01 05:00 [entrez]
AID - S0016508503012058 [pii]
AID - 10.1016/s0016-5085(03)01205-8 [doi]
PST - ppublish
SO  - Gastroenterology. 2003 Oct;125(4):1032-41. doi: 10.1016/s0016-5085(03)01205-8.