Association of rare SPINK1 gene mutation with another base substitution in chronic pancreatitis patients

• Published in: World journal of gastroenterology : WJG 2006-09, Vol.12 (33), p.5352-5356
• Main Authors: Kalinin, Viacheslav N, Kaifi, Jussuf T, Schwarzenbach, Heidi, Sergeyev, Anatoly S, Link, Bjoern C, Bogoevski, Dean, Vashist, Yogesh, Izbicki, Jakob R, Yekebas, Emre F
• Format: Article
• Language: English
• Subjects: 5' Untranslated Regions; Base Sequence; Carrier Proteins - genetics; Cohort Studies; DNA - metabolism; DNA Mutational Analysis; Family Health; Gene Expression Regulation; Genetic Predisposition to Disease; Haplotypes; Humans; Molecular Sequence Data; Mutation; Pancreatitis, Chronic - diagnosis; Pancreatitis, Chronic - genetics; Rapid Communication; Trypsin Inhibitor, Kazal Pancreatic; 基因突变; 慢性胰腺炎; 病理机制
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v12.i33.5352

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 patients.