POLYMORPHISM OF THE HEAT-SHOCK PROTEIN GENE <i>HSP70-2</i>IN SYSTEMIC LUPUS ERYTHEMATOSUS

Pablos, JL; Carreira, Patrícia; Martín-Villa, José Manuel; Montalvo, G.; Arnaiz‐Villena, A.; Gómez-Reino, Juan J.

doi:10.1093/rheumatology/34.8.721

Cited by 38 publications

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“…Thus, the chromosome mapping of the HSP family in the MHC class III region, the importance of HSPs in the immune response and the strong linkage disequilibrium with other significant MHC alleles highlights that the HSP70 genes may be associated with susceptibility for autoimmune diseases. The HSP70-2 gene polymorphism is associated with an increased risk of type I diabetes (19), systemic lupus erythematosus (18,26) and rheumatoid arthritis (27). The HSP70-2 polymorphism is a result of an A-G substitution in the coding sequence of the gene.…”

Section: Discussionmentioning

confidence: 99%

“…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 candidate gene in CD (16,17). Due to an A-G transition at the 1,267 position, the HSP70-2 gene has a PstI site (13,18) and different genotypes of the HSP70-2 gene have been shown to be associated with various levels of HSP70 mRNA expression (19). Single-nucleotide polymorphisms at the PstI site of nucleotide 1,267 have previously been found to be associated with intestinal perforation, abscess formation and fistula in Japanese and Caucasian patients with CD (16,17,20), suggesting that this …”

Section: Introductionmentioning

confidence: 99%

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Heat-shock protein 70-2 BB genotype is associated with reduced risks of the steroid-dependent and refractory phenotypes of ulcerative colitis

et al. 2014

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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...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Heat-shock protein 70-2 BB genotype is associated with reduced risks of the steroid-dependent and refractory phenotypes of ulcerative colitis

et al. 2014

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“…The present results do not support the findings in previous studies which have implicated HSP70-2 gene polymorphism in SLE and other autoimmune diseases. [4][5][6][7][8] However, in most of the cases, the associations were due to linkage disequilibrium between HSP70-2B and DR3 alleles [5][6][7] which are included in the A1-B8-DR3 and A30-B18-DR3 extended haplotypes and thus, probably secondary to, the DR/DQ associations. On the other hand, previous studies have failed to show significant relevance of HSP70 polymorphism in the susceptibility to several HLA-associated diseases.…”

Section: Discussionmentioning

confidence: 99%

“…7 This analysis was performed considering the polymorphic Pst I site at position 1267 of these alleles. We selected the following primers spanning the polymorphic Pst I site (nucleotide 1267) according to the previously described sequence, 7 sense (nucleotide 1083-1102 within the coding region) 5Ј-CATCGACTTCTACACGTCCA-3Ј and antisense (nucleotide 2180-2199 within the 3Ј untranslated end to avoid HSP70-1 homology) 5Ј-CAAAGTCC TTGAGTCCCAAC-3Ј.…”

Section: Pcr Analysis Of Hsp70-2 Allelesmentioning

confidence: 99%

“…3 Several studies have proposed the HSP's loci as possible susceptibility genes for the development of autoimmune diseases; ie, Grave's disease, 4 insulindependent diabetes mellitus, 5 celiac disease 6 and SLE. 7,8 In Spanish patients with SLE, the association was due to linkage disequilibrium between HSP70 and HLA-DR3, 7 whereas in African American patients the association was independent of this disequilibrium. 8 Since the linkage disequilibrium between HLA and HSP70-2 alleles has been described in Caucasian populations, studies in other populations are mandatory.…”

Section: Introductionmentioning

confidence: 99%

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Lack of association between the polymorphism at the heat-shock protein (HSP70-2) gene and systemic lupus erythematosus (SLE) in the Mexican Mestizo population

et al. 2000

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Major histocompatibility complex (MHC) alleles have been recognized as genetic factors for developing systemic lupus erythematosus (SLE). In the present study we analyzed whether a heat-shock protein gene (HSP70-2) is involved in determining susceptibility to develop SLE in a Mexican Mestizo population. A HSP70-2 Pst I polymorphism was detected by a restriction fragment length polymorphism analysis of polymerase chain reaction (PCR-RFLP) in 107 SLE patients and 158 healthy controls. No statistically significant differences were observed in the HSP70-2 allele distribution between patients and healthy controls. HLA-DR analysis showed an increased frequency of HLA-DR3 allele in the patients group (P Ͻ 0.05, OR = 2.26, EF = 6.0%). On the other hand, when we analyzed HSP70-2 polymorphism in relation to HLA-DR3 allele, we could only detect an increased frequency of AB genotype in the DR3 negative patients (pC Ͻ 0.05, RR = 2.6, EF = 11.3%). Linkage disequilibrium was observed for three haplotypes: HLA-DR3- HSP70

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Genetics of Systemic Lupus Erythematosus

Gulko¹,

Winchester²

1999

Lupus

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POLYMORPHISM OF THE HEAT-SHOCK PROTEIN GENE HSP70-2IN SYSTEMIC LUPUS ERYTHEMATOSUS

Cited by 38 publications

References 0 publications

Heat-shock protein 70-2 BB genotype is associated with reduced risks of the steroid-dependent and refractory phenotypes of ulcerative colitis

Heat-shock protein 70-2 BB genotype is associated with reduced risks of the steroid-dependent and refractory phenotypes of ulcerative colitis

Lack of association between the polymorphism at the heat-shock protein (HSP70-2) gene and systemic lupus erythematosus (SLE) in the Mexican Mestizo population

Genetics of Systemic Lupus Erythematosus

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