title: Autoimmune-associated HLA-B8-DR3 haplotypes in Asian Indians are unique in C4 complement gene copy numbers and HSP-2 1267A/G.
abstract: The classical AH8.1 (HLA-A1-B8-DR3-DQ2) is the most common Caucasian haplotype, associated with several autoimmune diseases, immunologic hyperreactivity and rapid progression to the acquired immunodeficiency syndrome. However, in Asian Indians, there are multiple unique B8-DR3 haplotypes that are associated with autoimmunity and differ significantly from the common Caucasian AH8.1. The Indian HLA-A1-B8-DR3 is therefore referred to as an AH8.1 variant. The aims of this study were to compare C4A and C4B copy numbers and to identify alleles in HSP70-2 and LTA in these haplotypes. The Indian B8-DR3 haplotypes differ from the Caucasian AH8.1 at C4A and HSP70-2 loci. The Indian B8-DR3 haplotypes have 1 copy each at C4A and C4B, while the Caucasian AH8.1 has 1 copy at C4B but no C4A gene. Moreover, the Indian and Caucasian B8-DR3 haplotypes had HSP70-2 1267 *A, and *G alleles, respectively. By contrast, the LTA 252 *G allele occurred both in the Indian and Caucasian haplotypes. The Indian haplotypes also contained Bf*F and TNF-308*G that were different from the Caucasian equivalents Bf*S and TNF-308*A. These differences and previous studies support the hypothesis that B8-DR3-DQ2 haplotypes in Asian Indian population might have originated independently of Caucasian AH8.1 selectively through recombination and mutations. Because autoimmune disease associations are shared among these otherwise diverse haplotypes, these data strongly suggest that some shared component(s) of all these associated haplotypes may be playing a key role in such associations.
authors.affiliation: Department of Transplant Immunology and Immunogenetics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India.
authors.forename: Gurvinder
authors.initials: G
authors.lastname: Kaur
authors.forename: Neeraj
authors.initials: N
authors.lastname: Kumar
authors.forename: Agnes
authors.initials: A
authors.lastname: Szilagyi
authors.forename: Bernadett
authors.initials: B
authors.lastname: Blasko
authors.forename: George
authors.initials: G
authors.lastname: Fust
authors.forename: Katalin
authors.initials: K
authors.lastname: Rajczy
authors.forename: Eva
authors.initials: E
authors.lastname: Pozsonyi
authors.forename: Adrienn
authors.initials: A
authors.lastname: Hosso
authors.forename: Gyozo
authors.initials: G
authors.lastname: Petranyi
authors.forename: Nikhil
authors.initials: N
authors.lastname: Tandon
authors.forename: Narinder
authors.initials: N
authors.lastname: Mehra
mesh_terms: D000483:Alleles; D001327:Autoimmune Diseases / Q000208:ethnology / Q000235:genetics* / Q000276:immunology; D015934:Complement C4a / Q000235:genetics*; D015935:Complement C4b / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D015795:HLA-B8 Antigen / Q000235:genetics*; D015803:HLA-DR3 Antigen / Q000235:genetics*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007194:India; D020641:Polymorphism, Single Nucleotide
chemical_list: D015795:HLA-B8 Antigen; D015803:HLA-DR3 Antigen; D018840:HSP70 Heat-Shock Proteins; C525621:HSPA1B protein, human; D015934:Complement C4a; D015935:Complement C4b