Association of HLA-DRB1*0401 allele with chronic pancreatitis.
BACKGROUND
Chronic pancreatitis (CP) is characterized by irreversible morphologic and functional alterations of the pancreas, clinically presenting with upper abdominal pain as well as exocrine and endocrine insufficiencies. According to a more recent hypothesis, the pathogenesis may involve genetic and immunologic factors.


OBJECTIVE
To investigate the major histocompatibility complex (MHC) genes as a genetic background of chronic pancreatitis.


METHODS
Allelic polymorphisms were investigated in the genes of the MHC region (HLA B, DRB, DQB) with PCR-based methodologies (PCR-SSP) in 56 patients with CP (44 males and 12 females) and 183 normal controls (78 males and 105 females) of the same ethnic group. All patients and controls gave their informed consent.


RESULTS
Among HLA-DRB1 genes, DRB1*04 was significantly higher in CP patients than in controls (26.78% versus 8.1%; pc < 0.003; OR = 4.1; CI = 1.85-9.06). DRB1*04 allele specificities in the DRB1*04-positive patients demonstrated significantly higher frequencies of DRB1*0401 allele (14.3% versus 1.1%; p = 0.00017; OR = 15.08; CI = 3.1-73.36). Neither HLA-B nor HLA-DQB1 associations with the disease were found.


CONCLUSIONS
This study supports a role of HLA-DRB1*0401 as a susceptibility factor for patients with CP. HLA DRB1*0401 contains the 70QKRAA74 amino acid sequence, which is also expressed by several human pathogens, including Epstein-Barr virus. T cells may be triggered in the pancreatic tissue upon exposure to foreign peptides similar enough to cross-react and to break immunologic tolerance.
Cavestro
Giulia M
GM
Department of Clinical Sciences, University of Parma, Parma, Italy. giuliamartina.cavestro@unipr.it
Frulloni
Luca
L
Neri
Tauro M
TM
Seghini
Pietro
P
Nouvenne
Antonio
A
Zanetti
Adele
A
Bovo
Paolo
P
Di Mario
Francesco
F
Okolicsanyi
Lajos
L
Cavallini
Giorgio
G
D000328:Adult; D000368:Aged; D002908:Chronic Disease; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D008297:Male; D008875:Middle Aged; D010195:Pancreatitis / Q000235:genetics* / Q000473:pathology
D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553505:HLA-DRB1*04:01 antigen; D004247:DNA