Genetic and functional analysis of pyroglutamyl-peptidase I in coeliac disease.
Coeliac disease (CD) is an enteropathy caused by an immune reaction towards wheat gluten and similar proteins from barley and rye. It was shown that some gluten peptides spontaneously form N-terminal L-pyroglutamate. This modification could potentially make gluten more resistant to proteolytic degradation within the intestine. Pyroglutamyl-peptidase I (PGPEPI) is an enzyme that hydrolytically removes the L-pyroglutamyl residues that render the modified proteins and peptides more sensitive to degradation by other proteases. Interestingly, we found that the PGPEP1 gene is located in a CD susceptibility locus. As an impaired enzyme function caused by genetic alterations might increase the amount of immunogenic gluten peptides, we conducted a comprehensive functional genomics analysis of PGPEP1, including DNA sequencing, genetic association testing, and quantifying RNA expression. We also determined the enzymatic activity of PGPEPI in duodenal biopsies. Our results uniformly indicate that PGPEP1 is not involved in the aetiology and pathology of CD.
Monsuur
Alienke J
AJ
Complex Genetics Section, DBG-Department of Medical Genetics, University Medical Centre, Utrecht, the Netherlands.
Stepniak
Dariusz
D
Diosdado
Begoña
B
Wapenaar
Martin C
MC
Mearin
Maria Luisa
ML
Koning
Frits
F
Wijmenga
Cisca
C
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D002446:Celiac Disease / Q000201:enzymology / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D011751:Pyroglutamyl-Peptidase I / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
D011751:Pyroglutamyl-Peptidase I