The major histocompatibility complex conserved extended haplotype 8.1 in AIDS-related non-Hodgkin lymphoma.
BACKGROUND
Two single nucleotide polymorphisms (SNPs) in adjacent genes, lymphotoxin alpha (LTA +252G, rs909253 A>G) and tumor necrosis factor (TNF -308A, rs1800629 G>A), form the G-A haplotype repeatedly associated with increased risk of non-Hodgkin lymphoma (NHL) in individuals uninfected with HIV-1. This association has been observed alone or in combination with human leukocyte antigens HLA-B*08 or HLA-DRB1*03 in the major histocompatibility complex (MHC). Which gene variant on this highly conserved extended haplotype (CEH 8.1) in whites most likely represents a true etiologic factor remains uncertain.


OBJECTIVE
We aimed to determine whether the reported association of the G-A haplotype of LTA-TNF with non-AIDS NHL also occurs with AIDS-related NHL.


METHODS
SNPs in LTA and TNF and in 6 other genes nearby were typed in 140 non-Hispanic European American pairs of AIDS-NHL cases and matched controls selected from HIV-infected men in the Multicenter AIDS Cohort Study.


RESULTS
The G-A haplotype and a 4-SNP haplotype in the neighboring gene cluster (rs537160 (A) rs1270942 (G), rs2072633 (A), and rs6467 (C)) were associated with AIDS-NHL (odds ratio = 2.7, 95% confidence interval: 1.5 to 4.8, P = 0.0009; and odds ratio = 3.2, 95% confidence interval: 1.6 to 6.6, P = 0.0008; respectively). These 2 haplotypes occur in strong linkage disequilibrium with each other on CEH 8.1.


CONCLUSIONS
The CEH 8.1-specific haplotype association of MHC class III variants with AIDS-NHL closely resembles that observed for non-AIDS NHL. Corroboration of an MHC determinant of AIDS and non-AIDS NHL alike would imply an important pathogenetic mechanism common to both.
Aissani
Brahim
B
Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL 35294-0022, USA. baissani@uab.edu
Ogwaro
Kisani M
KM
Shrestha
Sadeep
S
Tang
Jianming
J
Breen
Elizabeth C
EC
Wong
Hui-Lee
HL
Jacobson
Lisa P
LP
Rabkin
Charles S
CS
Ambinder
Richard F
RF
Martinez-Maza
Otoniel
O
Kaslow
Richard A
RA
D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006680:HLA Antigens / Q000235:genetics*; D006239:Haplotypes; D006630:Hispanic or Latino; D006801:Humans; D016483:Lymphoma, AIDS-Related / Q000235:genetics*; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics*; D008233:Lymphotoxin-alpha / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D006680:HLA Antigens; D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha