Relevance of variants in serum antiproteinases for the course of chronic pancreatitis.
BACKGROUND
Mutations of the pancreatic serine protease inhibitor, Kazal type 1 (SPINK1), the cationic trypsinogen (PRSS1) and the cystic fibrosis transmembrane conductance regulator (CFTR) were reported to be genetic risk factors of chronic pancreatitis (CP). The aim of this study was to determine the role of genetic variants of the main serum antiproteinases alpha-1-antitrypsin (AAT) and alpha-2-macroglobulin (A2M) for the course of chronic pancreatitis.


METHODS
124 patients with non-alcoholic chronic pancreatitis (with PRSS1 or SPINK1 mutations or idiopathic pancreatitis) and 64 healthy controls were investigated for the AAT mutations PiS and PiZ, and the PiM determining variants R101H, V213A, E376D. In 101 subjects, the 'bait region' of A2M was sequenced. A pentanucleotide deletion in the bait region of A2M was analysed in 147 chronic pancreatitis (CP) patients and 87 controls.


RESULTS
The lowest prevalences of V213A and E376D were found in PRSS1 patients, whereas an increased rate of these mutations was present in the SPINK1 group, and the highest prevalence was found in patients with idiopathic pancreatitis. The prevalence of PiM variants was higher in patients with early onset CP than in late onset (P < 0.05 for E376D). The coding region of the bait region of A2M was of wild type in all investigated subjects. The A2M pentanucleotide deletion showed a homogenous distribution in patients and controls.


CONCLUSIONS
Our study suggests a moderating, but not predominant, role of AAT variants in the course of chronic non-alcoholic pancreatitis.
Teich
N
N
Medizinische Klinik und Poliklinik II, Universitätsklinikum Leipzig, Germany. teichn@medizin.uni-leipzig.de
Walther
K
K
Bödeker
H
H
Mössner
J
J
Keim
V
V
D000293:Adolescent; D000328:Adult; D000368:Aged; D001483:Base Sequence; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010195:Pancreatitis / Q000175:diagnosis / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011336:Probability; D011379:Prognosis; D012680:Sensitivity and Specificity; D015842:Serine Proteinase Inhibitors / Q000097:blood / Q000235:genetics*; D012720:Severity of Illness Index; D014357:Trypsin; D014362:Trypsinogen / Q000032:analysis / Q000097:blood* / Q000235:genetics; D000515:alpha 1-Antitrypsin / Q000032:analysis / Q000235:genetics; D000511:alpha-Macroglobulins / Q000032:analysis / Q000235:genetics
D005819:Genetic Markers; D015842:Serine Proteinase Inhibitors; D000515:alpha 1-Antitrypsin; D000511:alpha-Macroglobulins; D014362:Trypsinogen; C489303:PRSS1 protein, human; D014357:Trypsin