Association of rare SPINK1 gene mutation with another base substitution in chronic pancreatitis patients.
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Association of rare SPINK1 gene mutation with another base substitution in chronic pancreatitis patients. / Kalinin, Viacheslav N; Kaifi, Jussuf; Schwarzenbach, Heidi; Sergeyev, Anatoly S; Link, Bjoern C; Bogoevski, Dean; Vashist, Yogesh; Izbicki, Jakob R; Yekebas, Emre F.
In: WORLD J GASTROENTERO, Vol. 12, No. 33, 33, 2006, p. 5352-5356.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Association of rare SPINK1 gene mutation with another base substitution in chronic pancreatitis patients.
AU - Kalinin, Viacheslav N
AU - Kaifi, Jussuf
AU - Schwarzenbach, Heidi
AU - Sergeyev, Anatoly S
AU - Link, Bjoern C
AU - Bogoevski, Dean
AU - Vashist, Yogesh
AU - Izbicki, Jakob R
AU - Yekebas, Emre F
PY - 2006
Y1 - 2006
N2 - 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.
AB - 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.
M3 - SCORING: Zeitschriftenaufsatz
VL - 12
SP - 5352
EP - 5356
JO - WORLD J GASTROENTERO
JF - WORLD J GASTROENTERO
SN - 1007-9327
IS - 33
M1 - 33
ER -