CAJ | 학술논문

AIM: To verify and expand the known spectrum of serine protease inhibitor Kazal type 1 (SPINK1) gene mutations in chronic pancreatitis.METHODS: DNA extracted from 172 chronic pancreatitis patients was assayed for SPINK1 gene mutations by PCR and DNA sequencing. A control cohort of 90 unrelated healthy individuals was analysed by the same methods for presence of common populational polymorphisms,and frequency of five-loci haplotypes was calculated. Linkages of gene aberrations in single SPINK1 gene copies were analysed by long-distance PCR followed by allele-specific PCR and DNA sequencing.RESULTS: The most frequent SPINK1 gene mutation N34S was found at a frequency of 6%. Furthermore, we detected the heterozygous intervening sequence (IVS)3 + 2 T ＞ C mutated gene in 2 German patients and 1 Macedonian chronic pancreatitis patient. In all three SPINK1 gene copies an additional rare base substitution was found: 5'untranslated region (UTR)-215 G ＞ A. Polymorphism analysis revealed that all three affected genes carried the same five-loci haplotype. DNA sequencing of another chronic pancreatitis-related gene PRSS1 (cationic trypsinogen) did not reveal any mutations in these 3 patients.CONCLUSION: We found in 3 (2%) of 172 chronic pancreatitis patients an IVS3 + 2 T ＞ C SPINK1 gene mutation and a base substitution 5'UTR-215 G ＞ A in the same gene copy. Most probably the 5'UTR-215 G ＞A represents a rare polymorphism and not a mutation as previously concluded. Haplotype analysis suggests a common origin of the IVS3 + 2 T ＞ C mutation in these patietts.