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 SPI...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-specifi c 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. Poly-morphism analysis revealed that all three affected genes carried the same fi ve-loci haplotype. DNA sequencing of another chronic pancreatitis-related gene PRSS1 (cationic trypsinogen) did not reveal any mutations in these 3 pa-tients.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 inthe same gene copy. Most probably the 5’UTR-215 G >A represents a rare polymorphism and not a mutationas previously concluded. Haplotype analysis suggests acommon origin of the IVS3 + 2 T > C mutation in thesepatients.展开更多
Objective In this study,mannan-binding lectin-associated serine protease 2(MASP2)gene variant was evaluated to assess the risk of radiation pneumonitis(RP)in patients with pulmonary malignancies.Methods A total of 169...Objective In this study,mannan-binding lectin-associated serine protease 2(MASP2)gene variant was evaluated to assess the risk of radiation pneumonitis(RP)in patients with pulmonary malignancies.Methods A total of 169 lung cancer patients with radiotherapy were included in our prospective study(NCT02490319)and genotyped using the Sanger sequencing method.Multivariate Cox hazards analysis and multiple testing were applied to estimate the hazard ratio(HR)and 95%confidence intervals(CIs)of all factors possibly associated with RP risk.Results Patients with mean lung disease≥15 Gy and V20≥24%had higher risk of RP≥grade 2 compared with their counterparts(HR=1.888,95%CI:1.186-3.004,P=0.007;HR=2.126,95%CI:1.338-3.378,P=0.001,respectively).Importantly,CC+CA genotype of MASP2:rs12711521 was strongly associated with an increased occurrence of RP≥grade 2(HR=1.949,95%CI:1.278-2.971,P=0.002).Conclusion MASP2:rs12711521 was found to be significantly associated with RP≥grade 2 in our cohort and may thus be one of the important predictors of severe RP before radiotherapy,if further validated in larger population.展开更多
基金Supported by research grants from the 'Werner Otto Stiftung e.V.
文摘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-specifi c 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. Poly-morphism analysis revealed that all three affected genes carried the same fi ve-loci haplotype. DNA sequencing of another chronic pancreatitis-related gene PRSS1 (cationic trypsinogen) did not reveal any mutations in these 3 pa-tients.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 inthe same gene copy. Most probably the 5’UTR-215 G >A represents a rare polymorphism and not a mutationas previously concluded. Haplotype analysis suggests acommon origin of the IVS3 + 2 T > C mutation in thesepatients.
基金Supported by grants from the National Natural Science Foundation of China(No.81773360,81700145).
文摘Objective In this study,mannan-binding lectin-associated serine protease 2(MASP2)gene variant was evaluated to assess the risk of radiation pneumonitis(RP)in patients with pulmonary malignancies.Methods A total of 169 lung cancer patients with radiotherapy were included in our prospective study(NCT02490319)and genotyped using the Sanger sequencing method.Multivariate Cox hazards analysis and multiple testing were applied to estimate the hazard ratio(HR)and 95%confidence intervals(CIs)of all factors possibly associated with RP risk.Results Patients with mean lung disease≥15 Gy and V20≥24%had higher risk of RP≥grade 2 compared with their counterparts(HR=1.888,95%CI:1.186-3.004,P=0.007;HR=2.126,95%CI:1.338-3.378,P=0.001,respectively).Importantly,CC+CA genotype of MASP2:rs12711521 was strongly associated with an increased occurrence of RP≥grade 2(HR=1.949,95%CI:1.278-2.971,P=0.002).Conclusion MASP2:rs12711521 was found to be significantly associated with RP≥grade 2 in our cohort and may thus be one of the important predictors of severe RP before radiotherapy,if further validated in larger population.
