Premium
Contribution of the CFTR gene, the pancreatic secretory trypsin inhibitor gene ( SPINK1 ) and the cationic trypsinogen gene ( PRSS1 ) to the etiology of recurrent pancreatitis
Author(s) -
Tzetis M,
Kaliakatsos M,
Fotoulaki M,
Papatheodorou A,
Doudounakis S,
Tsezou A,
Makrythanasis P,
Kanavakis E,
NousiaArvanitakis S
Publication year - 2007
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/j.1399-0004.2007.00788.x
Subject(s) - trypsinogen , pancreatitis , etiology , gene , trypsin , hereditary pancreatitis , pancreatic disease , medicine , endocrinology , pancreas , genetics , biology , biochemistry , enzyme
Acute recurrent/chronic pancreatitis (CP) is a complex multigenic disease. This is a case–control study consisting of 25 Greek patients with CP and a control population of 236 healthy Greek subjects. The whole coding area and neighboring intronic regions of the three genes were screened. Seventeen of 25 patients (68%) had mutations in the cystic fibrosis transmembrane conductance regulator ( CFTR ) gene: nine compound heterozygotes with either mild or severe mutations and eight heterozygotes. Four patients (16%) carried CFTR‐modulating haplotypes V470‐TG11‐T5 and V470‐TG12‐T7. All were negative for PRSS1 gene mutations, while variants c.486C/T and c.738C/T were found in nine patients each, three homozygotes for the minor alleles. Two carried SPINK1 gene mutation p.N34S, one being transheterozygote with CFTR mutation p.F1052V. The promoter variant −253T>C was found in four individuals (one homozygous for the minor allele), all four being transheterozygotes with mutations in the CFTR gene as well. Finally two carried c.272C/T in the 3′ untranslated region, one being a p.N34S carrier as well. In total, 80% (20/25) of patients had a molecular defect in one or both of the CFTR and SPINK1 genes, suggesting that mutations/variants in the CFTR plus or minus mutations in the SPINK1 , but not the PRSS1 gene, may confer a high risk for recurrent pancreatitis.