Genetic Susceptibility in Acute Pancreatitis: Genotyping of GSTM1, GSTT1, GSTP1, CASP7, CASP8, CASP9, CASP10, LTA, TNFRSF1B, and TP53 Gene Variants

Genetic testing could play a critical role in diagnosis and prognosis of acute pancreatitis (AP) and guide effective therapeutic interventions. We hypothesized that genetic polymorphisms in apoptosis and oxidative stress genes could determine incidence or severity in AP. We conducted a hospital-base...

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Bibliographic Details
Published in:	Pancreas Vol. 46; no. 1; pp. 71 - 76
Main Authors:	Dʼ Oliveira Martins, Francisco, Gomes, Bruno Costa, Rodrigues, António Sebastião, Rueff, José
Format:	Journal Article
Language:	English
Published:	United States 01-01-2017
Subjects:	Acute Disease Adult Aged Case-Control Studies Caspases - genetics European Continental Ancestry Group - genetics Female Gene Frequency Genetic Predisposition to Disease - ethnology Genetic Predisposition to Disease - genetics Genotype Glutathione Transferase - genetics Humans Isoenzymes - genetics Male Middle Aged Pancreatitis - ethnology Pancreatitis - genetics Polymorphism, Single Nucleotide Portugal Receptors, Tumor Necrosis Factor, Type II - genetics Risk Factors Tumor Suppressor Protein p53 - genetics
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Summary:	Genetic testing could play a critical role in diagnosis and prognosis of acute pancreatitis (AP) and guide effective therapeutic interventions. We hypothesized that genetic polymorphisms in apoptosis and oxidative stress genes could determine incidence or severity in AP. We conducted a hospital-based case-control study in a white Portuguese population (133 AP patients and 232 age- and sex-matched healthy controls) to evaluate the role of 15 gene polymorphisms (2 deletions and 13 single nucleotide polymorphisms [SNPs]) in oxidative stress (GSTM1, GSTT1, GSTP1) and apoptosis genes (CASP7, CASP8, CASP9, CASP10, LTA, TNFRSF1B, TP53) in AP. Criteria for AP were abdominal pain, hyperamylasemia, and contrast-enhanced computed tomography. The presence of GSTM1 is associated with increased susceptibility for AP, and the GSTP1 Val105Ile SNP is associated with an increased risk for AP in men. CASP9 Phe136Leu/Phe136Phe SNPs (heterozygotes) increases the risk for mild AP (odds ratio, 3.616; 95% confidence interval, 1.151-11.364; P < 0.05), whereas the homozygotic genotype of CASP9 Ala28Val decreases risk for mild AP (odds ratio, 0.296; 95% confidence interval, 0.091-0.963; P < 0.05). Our results suggest that variations in GSTM1, GSTP1, and CASP9 may influence risk for AP.
ISSN:	0885-3177 1536-4828
DOI:	10.1097/MPA.0000000000000707