Progression of HIV-related disease is associated with HLA DQ and DR alleles defined by restriction fragment length polymorphisms.
A cohort of 139 hemophiliacs was typed for HLA D region genes by means of restriction fragment length polymorphisms (RFLPs) detected by HLA DQ and DR gene probes. Disease progression was studied in the 65 HIV antibody-positive patients, who were infected by contaminated clotting factor before 1985. Strong associations were found between disease progression in HIV-infected patients and allelic DNA fragments revealed by a DQ alpha cDNA probe. A 5.5 kb fragment was reduced in frequency and a 4.6 kb fragment increased in frequency (p less than 0.005) in the faster progressing group, as measured both by development of CDC Category IV clinical symptoms and CD4 number less than 200 x 10(6)/l. These results correlate with DR types deduced from the RFLP patterns revealed by DR beta and DQ alpha gene probes. A decrease in DR4 and an increase in both DR5 and the DR3 subtype found in the A1 B8 DR3 haplotype were associated with disease progression (p less than 0.05).
School of Biological Sciences, Macquarie University, Sydney, Australia.
J A
JA
Donald
K
K
Rudman
D W
DW
Cooper
K W
KW
Baumgart
R J
RJ
Garsia
P A
PA
Gatenby
K A
KA
Rickard
D000483:Alleles; D001778:Blood Coagulation Disorders / Q000150:complications / Q000235:genetics / Q000276:immunology; D015331:Cohort Studies; D004247:DNA / Q000235:genetics; D004198:Disease Susceptibility / Q000276:immunology; D005787:Gene Frequency; D005802:Genes, MHC Class II; D020022:Genetic Predisposition to Disease; D015658:HIV Infections / Q000150:complications / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D006683:HLA-DQ Antigens / Q000032:analysis* / Q000235:genetics; D006684:HLA-DR Antigens / Q000032:analysis* / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D012150:Polymorphism, Restriction Fragment Length; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D012720:Severity of Illness Index
D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D004247:DNA