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.
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-infectedmen 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.
Authors: Paul I W de Bakker; Roman Yelensky; Itsik Pe'er; Stacey B Gabriel; Mark J Daly; David Altshuler Journal: Nat Genet Date: 2005-10-23 Impact factor: 38.330
Authors: Theresa A Aly; Elise Eller; Akane Ide; Katherine Gowan; Sunanda R Babu; Henry A Erlich; Marian J Rewers; George S Eisenbarth; Pamela R Fain Journal: Diabetes Date: 2006-05 Impact factor: 9.461
Authors: Wade P Smith; Quyen Vu; Shuying Sue Li; John A Hansen; Lue Ping Zhao; Daniel E Geraghty Journal: Genomics Date: 2006-01-23 Impact factor: 5.736
Authors: E Louis; D Franchimont; A Piron; Y Gevaert; N Schaaf-Lafontaine; S Roland; P Mahieu; M Malaise; D De Groote; R Louis; J Belaiche Journal: Clin Exp Immunol Date: 1998-09 Impact factor: 4.330
Authors: C Andrew Stewart; Roger Horton; Richard J N Allcock; Jennifer L Ashurst; Alexey M Atrazhev; Penny Coggill; Ian Dunham; Simon Forbes; Karen Halls; Joanna M M Howson; Sean J Humphray; Sarah Hunt; Andrew J Mungall; Kazutoyo Osoegawa; Sophie Palmer; Anne N Roberts; Jane Rogers; Sarah Sims; Yu Wang; Laurens G Wilming; John F Elliott; Pieter J de Jong; Stephen Sawcer; John A Todd; John Trowsdale; Stephan Beck Journal: Genome Res Date: 2004-05-12 Impact factor: 9.043