Population-based case-control study of alpha 1-antitrypsin and SLC11A1 in Crohn's disease and ulcerative colitis.
BACKGROUND
Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases of the digestive tract. Genetic factors and an abnormal immune response to infections are suspected to be involved in inflammatory bowel diseases.


METHODS
In the present study 300 blood samples from CD patients (n = 100), UC patients (n = 100), and healthy controls (n = 100) were taken from a population-based case-control study. PCR assays and capillary electrophoresis were used to detect alpha 1 antitrypsin M, S, and Z alleles and the C-to-T transition at the -237 nucleotide position of the SLC11A1 promoter. Additionally, length polymorphism of (gt)n alleles in the promoter region and TGTG and CAAA insertion/deletion in the untranslated region (3' UTR) of the SLC11A1 gene were evaluated.


RESULTS
The Z allele only for AAT was associated (P < 0.05) with CD. No other significant results were detected for AAT alleles. For SLC11A1, alleles 1 and 2 were significant (P < 0.05) for UC, but only allele 3 was significant (P < 0.05) for CD. There was a significant (P < 0.05) association of a CAAA insertion with CD but not for deletion in the 3' UTR. No differences (P < 0.05) were detected for TAAA.


CONCLUSIONS
Because AAT and SLC11A1 proteins directly or indirectly function as inhibitors of human leukocyte elastase, mutations in the AAT and SLC11A1 genes may change the balance between elastase produced by leukocytes during phagocytosis.
Kotlowski
Roman
R
Department of Animal Science, University of Manitoba, Winnipeg, Manitoba, Canada.
Bernstein
Charles N
CN
Silverberg
Mark S
MS
Krause
Denis O
DO
D000328:Adult; D016022:Case-Control Studies; D027682:Cation Transport Proteins / Q000235:genetics*; D003093:Colitis, Ulcerative / Q000235:genetics*; D003424:Crohn Disease / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011401:Promoter Regions, Genetic; D000515:alpha 1-Antitrypsin / Q000235:genetics*; D000099173:Natural Resistance-associated Macrophage Protein 1
D027682:Cation Transport Proteins; D000515:alpha 1-Antitrypsin; D000099173:Natural Resistance-associated Macrophage Protein 1