Connections Between Genetics and Clinical Data: Role of MCP-1, CFTR, and SPINK-1 in the Setting of Acute, Acute Recurrent, and Chronic Pancreatitis.
Articolo
Data di Pubblicazione:
2010
Abstract:
Abstract
OBJECTIVES: Acute, acute recurrent, and chronic pancreatitis are infl ammatory diseases with multifactorial
pathogenic mechanisms. Genetic mutations and polymorphisms have been correlated with
pancreatitis. The aim of this study was to investigate the association of cystic fi brosis transmembrane
conductance regulator (CFTR) and serine protease inhibitor Kazal type 1 (SPINK-1)
gene mutations and monocyte chemoattractant protein 1 (MCP-1) – 2518A / G polymorphism with
acute pancreatitis (AP), acute recurrent pancreatitis (ARP), and chronic pancreatitis (CP), and to
associate genetic backgrounds with clinical phenotype in these three conditions.
METHODS: One hundred eighteen AP, 64 ARP, 142 CP patients, and 88 normal controls were enrolled
consecutively. We analyzed MCP-1 serum levels using enzyme-linked immunosorbent assay.
Polymorphism − 2518 of MCP-1 and SPINK-1 N34S gene mutations were determined by PCR –
restriction-fragment length polymorphism. Sequence analysis was performed when necessary.
Thirty-three CFTR mutations were analyzed in CP and ARP patients using multiplex DNA testing.
RESULTS: Serum MCP-1 levels were signifi cantly higher in all patients affected by pancreatic infl ammatory
diseases. Moreover, we found a signifi cant over-representation of the MCP-1G allele in ARP
patients. We found a statistically signifi cant association of CFTR gene mutations with ARP, but
not with CP. We did not fi nd a statistically signifi cant association of ARP or CP with the N34S
SPINK-1 gene mutation. Interestingly, 39 of 64 ARP patients (61 % ) carried at least one genetic
mutation and / or polymorphism. Five of 64 ARP patients had pancreas divisum and four of these
fi ve also carried the G allele.
CONCLUSIONS: Analysis of a comprehensive range of potential susceptibility variants is needed to support
modeling of the effects of genes and environment in pancreatitis. As such, beyond gene
mutations, the context within which those mutations exist must be considered. In pancreatitis
the context includes the infl ammatory response, clinical features, and exogenous factors.
OBJECTIVES: Acute, acute recurrent, and chronic pancreatitis are infl ammatory diseases with multifactorial
pathogenic mechanisms. Genetic mutations and polymorphisms have been correlated with
pancreatitis. The aim of this study was to investigate the association of cystic fi brosis transmembrane
conductance regulator (CFTR) and serine protease inhibitor Kazal type 1 (SPINK-1)
gene mutations and monocyte chemoattractant protein 1 (MCP-1) – 2518A / G polymorphism with
acute pancreatitis (AP), acute recurrent pancreatitis (ARP), and chronic pancreatitis (CP), and to
associate genetic backgrounds with clinical phenotype in these three conditions.
METHODS: One hundred eighteen AP, 64 ARP, 142 CP patients, and 88 normal controls were enrolled
consecutively. We analyzed MCP-1 serum levels using enzyme-linked immunosorbent assay.
Polymorphism − 2518 of MCP-1 and SPINK-1 N34S gene mutations were determined by PCR –
restriction-fragment length polymorphism. Sequence analysis was performed when necessary.
Thirty-three CFTR mutations were analyzed in CP and ARP patients using multiplex DNA testing.
RESULTS: Serum MCP-1 levels were signifi cantly higher in all patients affected by pancreatic infl ammatory
diseases. Moreover, we found a signifi cant over-representation of the MCP-1G allele in ARP
patients. We found a statistically signifi cant association of CFTR gene mutations with ARP, but
not with CP. We did not fi nd a statistically signifi cant association of ARP or CP with the N34S
SPINK-1 gene mutation. Interestingly, 39 of 64 ARP patients (61 % ) carried at least one genetic
mutation and / or polymorphism. Five of 64 ARP patients had pancreas divisum and four of these
fi ve also carried the G allele.
CONCLUSIONS: Analysis of a comprehensive range of potential susceptibility variants is needed to support
modeling of the effects of genes and environment in pancreatitis. As such, beyond gene
mutations, the context within which those mutations exist must be considered. In pancreatitis
the context includes the infl ammatory response, clinical features, and exogenous factors.
Tipologia CRIS:
1.1 Articolo in rivista
Elenco autori:
Cavestro, GIULIA MARTINA; Ra, Zuppardo; S., Bertolini; G., Sereni; L., Frulloni; S., Okolicsanyi; C., Calzolari; Sk, Singh; M., Sianesi; P., Del Rio; G., Leandro; A., Franzè; F., Di Mario
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