SNP screening of central MHC-identified HLA-DMB as a candidate susceptibility gene for HIV-related Kaposi's sarcoma

B. Aissani, A. K. Boehme, H. W. Wiener, S. Shrestha, Lisa Paula Jacobson, R. A. Kaslow

Research output: Contribution to journalArticle

Abstract

The major histocompatibility complex (MHC) region on chromosome 6p21.3 is suspected to host susceptibility loci for HIV-related Kaposi's sarcoma (HIV-KS). A nested case-control study in the Multicenter AIDS Cohort Study was designed to conduct fine genetic association mapping across central MHC. Individuals co-infected with HIV-1 and human herpes virus-8 who later developed KS were defined as cases (n=354) and were matched 1:1 with co-infected KS-free controls. We report data for new independent MHC class II and III susceptibility loci. In particular, class II HLA-DMB emerged as a strong candidate, with the intronic variant rs6902982 A>G associated with a fourfold increase of risk (odds ratio (OR)=4.09; 95% confidence interval (CI)=1.90-8.80; P=0.0003). A striking multiplicative effect on the estimated risk was associated with further carriage of two non-synonymous variants, rs1800453 A>G (Asp697Gly) and rs4148880 A>G (Ile393Val), in the linked TAP1 gene (OR=10.5; 95% CI=2.54-43.6; P=0.0012). The class III susceptibility variant is moderately associated with HIV-KS and lies within a 120-kb-long haplotype (OR=1.52; 95% CI=1.01-2.28; P=0.047) formed by rs7029 A>G (GPANK1 3' untranslated region), rs1065356 G>A (LY6G6C), rs3749953 A>G (MSH5-SAPCD1 read through) and rs707926 G>A (VARS). Our data suggest that antigen processing by MHC class II molecules is a target pathway in the pathogenesis of HIV-KS.

Original languageEnglish (US)
Pages (from-to)424-429
Number of pages6
JournalGenes and Immunity
Volume15
Issue number6
DOIs
StatePublished - Sep 1 2014

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Kaposi's Sarcoma
Major Histocompatibility Complex
Single Nucleotide Polymorphism
Odds Ratio
HIV
Confidence Intervals
Genes
Antigen Presentation
3' Untranslated Regions
Haplotypes
HIV-1
Case-Control Studies
Acquired Immunodeficiency Syndrome
Cohort Studies
Chromosomes
Viruses
HLA-DM antigens

ASJC Scopus subject areas

  • Medicine(all)

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SNP screening of central MHC-identified HLA-DMB as a candidate susceptibility gene for HIV-related Kaposi's sarcoma. / Aissani, B.; Boehme, A. K.; Wiener, H. W.; Shrestha, S.; Jacobson, Lisa Paula; Kaslow, R. A.

In: Genes and Immunity, Vol. 15, No. 6, 01.09.2014, p. 424-429.

Research output: Contribution to journalArticle

Aissani, B. ; Boehme, A. K. ; Wiener, H. W. ; Shrestha, S. ; Jacobson, Lisa Paula ; Kaslow, R. A. / SNP screening of central MHC-identified HLA-DMB as a candidate susceptibility gene for HIV-related Kaposi's sarcoma. In: Genes and Immunity. 2014 ; Vol. 15, No. 6. pp. 424-429.
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abstract = "The major histocompatibility complex (MHC) region on chromosome 6p21.3 is suspected to host susceptibility loci for HIV-related Kaposi's sarcoma (HIV-KS). A nested case-control study in the Multicenter AIDS Cohort Study was designed to conduct fine genetic association mapping across central MHC. Individuals co-infected with HIV-1 and human herpes virus-8 who later developed KS were defined as cases (n=354) and were matched 1:1 with co-infected KS-free controls. We report data for new independent MHC class II and III susceptibility loci. In particular, class II HLA-DMB emerged as a strong candidate, with the intronic variant rs6902982 A>G associated with a fourfold increase of risk (odds ratio (OR)=4.09; 95{\%} confidence interval (CI)=1.90-8.80; P=0.0003). A striking multiplicative effect on the estimated risk was associated with further carriage of two non-synonymous variants, rs1800453 A>G (Asp697Gly) and rs4148880 A>G (Ile393Val), in the linked TAP1 gene (OR=10.5; 95{\%} CI=2.54-43.6; P=0.0012). The class III susceptibility variant is moderately associated with HIV-KS and lies within a 120-kb-long haplotype (OR=1.52; 95{\%} CI=1.01-2.28; P=0.047) formed by rs7029 A>G (GPANK1 3' untranslated region), rs1065356 G>A (LY6G6C), rs3749953 A>G (MSH5-SAPCD1 read through) and rs707926 G>A (VARS). Our data suggest that antigen processing by MHC class II molecules is a target pathway in the pathogenesis of HIV-KS.",
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