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. 2009 Oct 1;52(2):170-9.
doi: 10.1097/QAI.0b013e3181b017d5.

The major histocompatibility complex conserved extended haplotype 8.1 in AIDS-related non-Hodgkin lymphoma

Brahim Aissani  1 , Kisani M Ogwaro, Sadeep Shrestha, Jianming Tang, Elizabeth C Breen, Hui-Lee Wong, Lisa P Jacobson, Charles S Rabkin, Richard F Ambinder, Otoniel Martinez-Maza, Richard A Kaslow
Affiliations

The major histocompatibility complex conserved extended haplotype 8.1 in AIDS-related non-Hodgkin lymphoma

Brahim Aissani et al. J Acquir Immune Defic Syndr. .

Abstract

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.

Conclusion: 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.

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