Abstract. Previous studies have demonstrated the protective role of inducible heat-shock protein (HSP) 70 in intestinal cells. The HSP70-2 gene has a PstI site due to an A-G transition at the 1,267 position and different genotypes are associated with various levels of mRNA expression. The present study aimed to clarify the effect of the HSP70-2 polymorphism on the risk of ulcerative colitis (UC), including its clinical phenotypes. A total of 121 patients with UC and 500 healthy control (HC) subjects participated in the study. To assess the polymorphisms at the 1,267 position of the HSP70-2 gene, restriction fragment length polymorphism analysis was performed. The subjects in the study were classified by disease behavior, severity and extent of disease. Although no significant difference of the HSP70-2 genotype distribution was identified between the HC and UC groups, the BB genotype exhibited a lower risk of the steroid-dependent phenotype [odds ratio (OR), 0.12; 95% confidence interval (CI), 0.02-0.95; P=0.02]. The same genotype was also associated with a lower risk of the refractory phenotype (OR, 0.16; 95% CI, 0.04-0.73; P= 0.01). There was no direct correlation between the polymorphism of the HSP70-2 gene and UC susceptibility. However, there was an association between a reduced risk of the steroid-dependent and refractory phenotypes of UC and the BB genotype.
IntroductionUlcerative colitis (UC) is a condition that affects the colon and rectum and usually involves the innermost lining mucosa. The condition presents as continuous areas of inflammation, with no segments of normal mucosa (1). UC is characterized by chronic, relapsing colonic inflammation with an unknown etiology. Immune dysregulation and genetic factors are known to play important roles in the pathogenesis of UC.UC is a multifactorial, polygenic disease with possible genetic heterogeneity, and different genetic backgrounds may account for the numerous clinical patterns of UC (2,3). Epidemiological studies and genome-wide linkage analyses have established the genetic predisposition to inflammatory bowel diseases, however, information is lacking with regard to the genes that are responsible (4). Therefore, the association between the polymorphism of various genes and UC has been previously studied (5-11).Heat-shock proteins (HSPs), in particular the HSP70 family, play important roles in intracellular trafficking and conformation of proteins by acting as a molecular chaperone, thus involving them in immune regulation (12). Three members of the HSP gene, known as HSP70-1, -2 and-Hom, have been mapped to the class-III region of the human major histocompatibility complex (MHC); 92 kb telomeric of the complement C2 locus (13). HSP70-1 and -2 encode the same protein, known as inducible HSP70. A previous study showed the protective role of inducible HSP70 in intestinal cells (14). HSP70 was also detected in the inflamed colonic mucosa of Crohn's disease (CD) patients (15), and therefore, the HSP70 gene family has been suggested to be a possible candidat...