Heat-shock protein 70-1 and HLA class II gene polymorphisms associated with celiac disease susceptibility in Navarra (Spain).
Heat shock proteins (HSP) are thought to play a role in the immune response making probable their contribution to celiac disease (CD). We studied the polymorphisms in the 5' regulatory region of the HSP70-1 gene and performed genomic HLA-DQ and -DR typing in 128 CD patients and 94 healthy controls from Navarra (Spain). The frequency of the C allele of the HSP70-1, characterized by the intermediate electrophoretic mobility of DNA, was significantly increased among CD patients (64.5% vs 37.2%. p <1 x 10(-7)). When subjects were stratified by the HLA II genotype, differences were statistically significant between DR3-negative or DR3-DQB1*02-negative CD patients and matched controls. Homozygosity for the DQB1*02 allele was present in 48.4% of CD patients and 12.8% of controls (OR = 6.4; CI:3.1 to 13.8; p <1 x 10(-7)). Similar increased risk was observed for DQB1*02/*02, DRB1*03/-, or DRB1*03/07 patients. Furthermore, those individuals expressing the classical HLA alleles in CD (DQB1*02/*02, DRB1*03/*07) who also carried the HSP70-1 CC genotype were twelve times more likely to develop the disease than the matched controls. We therefore conclude that although HSP70-1 gene does not seem to be primarily associated with CD, it might be a component of the high risk haplotype, playing a role as an additional predisposing gene for the disease.
Ramos-Arroyo
M A
MA
Servicios de Genética, Hospital Virgen del Camino, Pamplona, Spain. ma.ramos.arroyo@cfnavarra.es
Feijoó
E
E
Sánchez-Valverde
F
F
Aranburu
E
E
Irisarri
N
N
Olivera
J E
JE
Valiente
A
A
D020121:5' Untranslated Regions / Q000235:genetics; D000483:Alleles; D002446:Celiac Disease / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006683:HLA-DQ Antigens / Q000235:genetics; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D006579:Heterozygote; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006801:Humans; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D015800:Protozoan Proteins / Q000235:genetics*; D013030:Spain
D020121:5' Untranslated Regions; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D018840:HSP70 Heat-Shock Proteins; D000949:Histocompatibility Antigens Class II; D015800:Protozoan Proteins; C081884:heat-shock protein 70.1