Changes In Activity of HSPA1A and HSPA1L is Associated with Early Acute Pancreatitis Severity

Abstract

Introduction: Genome assessment shows promise as a potential method for predicting acute pancreatitis (AP) severity. We hypothesized that Heat Shock Protein 70 (HSP70) single nucleotide polymorphisms (SNPs) and expression changes may play a role in early detection of acute pancreatitis severity. Methods: A total of 57 AP patients and 52 age- and sex-matched healthy controls were studied. Peripheral blood samples from pancreatitis patients were collected upon admission. Two SNPs of the HSP70-gene family were selected. RNA was extracted parallel to genomic DNA from AP patients (N=12) and healthy controls (N=21).Gene expression of two HSP70 family members HSPA1A and HSPA1L was measured using TaqMan gene expression assays via reverse transcription quantitative polymerase chain reaction (RT-qPCR). Results: Major allele frequency in HSPA1A gene was 1 (A>G) for AP patients and 1 (A>G) for controls. For HSPA1A, the gene major allele frequency was 0.672 (A>C) for patients and 0.7 (A>C) for controls, the major allele frequencies were 0.638 (A>G) and 0.672 (G>C) for patients and 0.85 (A>G) and 0.65 (G>C) for controls, respectively. The allele frequencies differed between AP patients with organ failure and those with mild disease. Following gene expression of HSPA1L and SNP relationship analysis, AP patients with heterozygous genotype had higher expression levels as compared to non-AP patients (p=0.014). Conclusions: Our data suggest that polymorphism of the HSP70 promoter region may be a risk factor for developing severe acute pancreatitis. Further study to determine the urine levels of HSP70 protein expression is needed to confirm the protective mechanism of HSP70.