title: Polymorphism in heat-shock protein 70-1 (HSP70-1) gene promoter region and susceptibility to tuberculoid leprosy and pulmonary tuberculosis in Asian Indians.
abstract: Heat shock proteins (HSP) act as immunological target structures either by themselves because of an unusual expression pattern, or they are carrier proteins for immunogenic peptides. A three-allele polymorphism of HSP70-1 promoter region was analysed in random patients with pulmonary tuberculosis (PTB), or with tuberculoid (TT) leprosy and healthy controls from North India. HSP70-1A and HSP70-1C occurred more frequently (> 60%) while HSP70-1B occurred infrequently in this population. Only HSP70-1A allele was significantly increased in TT leprosy as compared to healthy controls (91.8% Vs 71.1%, Pc < 0.03, RR = 4.58). Although a strong association of HLA-DR15 was observed with both of these patient groups in earlier studies, no correlation was found between HSP70-1 promoter alleles with any of the HLA allotypes. Amongst six possible genotype combinations of HSP70-1 promoter allele, only four (A/A, A/B, A/C, C/C) were encountered in Asian Indians. A significant increase of HSP70-1 A/C genotype was observed among DR15 negative PTB patients as compared to DR15 negative controls (87.5% Vs 35.7%, X2 = 8.6, Pc < 0.02) giving highest relative risk of 12.6. These findings suggest that HSP70-1 genes may play a secondary role to HLA-DR in governing susceptibility to mycobacterial infectious diseases.
authors.affiliation: Department of Histocompatibility and Immunogenetics, All India Institute of Medical Sciences, New Delhi 110 029, India. lingam@cmgm.stanford.edu
authors.forename: R
authors.initials: R
authors.lastname: Rajalingam
authors.forename: N K
authors.initials: NK
authors.lastname: Mehra
authors.forename: D P
authors.initials: DP
authors.lastname: Singal
mesh_terms: D000328:Adult; D001483:Base Sequence; D016022:Case-Control Studies; D017931:DNA Primers / Q000235:genetics; D005260:Female; D006680:HLA Antigens / Q000235:genetics; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D007194:India; D015441:Leprosy, Tuberculoid / Q000235:genetics* / Q000276:immunology; D008297:Male; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D014397:Tuberculosis, Pulmonary / Q000235:genetics* / Q000276:immunology
chemical_list: D017931:DNA Primers; D006680:HLA Antigens; D018840:HSP70 Heat-Shock Proteins