title: Associations of MHC ancestral haplotypes with resistance/susceptibility to AIDS disease development.
abstract: We tested the association of MHC ancestral haplotypes with rapid or slow progression to AIDS by comparing their frequencies in the French genetics of resistance/susceptibility to immunodeficiency virus cohort with that reported in a control French population. Seven ancestral haplotypes were identified in the genetics of resistance/susceptibility to immunodeficiency virus cohort with a frequency >1%. The 8.1 (odds ratio (OR) = 3, p = 0.006), 35.1 (OR = 5.7, p = 0.001), and 44.2 (OR = 3.4, p = 0.007) ancestral haplotypes were associated with rapid progression, whereas the 35.2 (OR = 3.6, p = 0.001), 44.1 (OR = 5.4, p < 10(-4)), and 57.1 (OR = 5.8, p < 10(-4)) ancestral haplotypes were associated with slow progression to AIDS. Although the frequency of each ancestral haplotype is low in the population, the OR were quite higher than those previously obtained for single HLA allele associations, with some p values as low as 10(-4). The analysis of the recombinant fragments of these haplotypes allowed the identification of the MHC regions in the 35.1, 35.2, and 44.2 haplotypes associated with rapid progression to AIDS and the MHC regions of the 44.1 and 57.1 haplotypes associated with slow progression to AIDS. Previous studies have identified single HLA alleles associated with disease progression. Our results on recombinant fragments confirm the direct role of HLA-B35 in rapid progression. Associations with HLA-A29 and -B57 might be due to linkage disequilibrium with other causative genes within the MHC region.
authors.affiliation: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Dana Building, Room 1514, Boston, MA 02115, USA. pedro_flores-villanueva@dfci.harvard.edu
authors.forename: Pedro O
authors.initials: PO
authors.lastname: Flores-Villanueva
authors.forename: Houria
authors.initials: H
authors.lastname: Hendel
authors.forename: Sophie
authors.initials: S
authors.lastname: Caillat-Zucman
authors.forename: Jay
authors.initials: J
authors.lastname: Rappaport
authors.forename: Alberto
authors.initials: A
authors.lastname: Burgos-Tiburcio
authors.forename: Sebastien
authors.initials: S
authors.lastname: Bertin-Maghit
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Ruiz-Morales
authors.forename: Maria E
authors.initials: ME
authors.lastname: Teran
authors.forename: Juan
authors.initials: J
authors.lastname: Rodriguez-Tafur
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Zagury
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics* / Q000276:immunology*; D000483:Alleles; D015331:Cohort Studies; D018450:Disease Progression; D005787:Gene Frequency / Q000276:immunology; D020022:Genetic Predisposition to Disease; D006680:HLA Antigens / Q000032:analysis / Q000235:genetics*; D015234:HLA-A Antigens / Q000235:genetics; D015235:HLA-B Antigens / Q000235:genetics; D015236:HLA-C Antigens / Q000235:genetics; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006239:Haplotypes / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000032:analysis / Q000235:genetics; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics
chemical_list: D006680:HLA Antigens; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A