Genome-wide association study on the development of cross-reactive neutralizing antibodies in HIV-1 infected individuals.
Broadly neutralizing antibodies may protect against HIV-1 acquisition. In natural infection, only 10-30% of patients have cross-reactive neutralizing humoral immunity which may relate to viral and or host factors. To explore the role of host genetic markers in the formation of cross-reactive neutralizing activity (CrNA) in HIV-1 infected individuals, we performed a genome-wide association study (GWAS), in participants of the Amsterdam Cohort Studies with known CrNA in their sera. Single-nucleotide polymorphisms (SNPs) with the strongest P-values are located in the major histocompatibility complex (MHC) region, close to MICA (P = 7.68 × 10(-7)), HLA-B (P = 6.96 × 10(-6)) and in the coding region of HCP5 (P = 1.34 × 10(-5)). However, none of the signals reached genome-wide significance. Our findings underline the potential involvement of genes close or within the MHC region with the development of CrNA.
Department Experimental Immunology, Sanquin Research, Landsteiner Laboratory, and Center for Infectious Diseases and Immunity Amsterdam, Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands.
Zelda
Z
Euler
Marit J
MJ
van Gils
Brigitte D
BD
Boeser-Nunnink
Hanneke
H
Schuitemaker
Daniëlle
D
van Manen
D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology*; D018791:CD4 Lymphocyte Count; D016000:Cluster Analysis; D003429:Cross Reactions / Q000235:genetics* / Q000276:immunology*; D055106:Genome-Wide Association Study; D015483:HIV Antibodies / Q000097:blood / Q000276:immunology*; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology; D006716:Homosexuality; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000276:immunology; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D019562:Viral Load
D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D006680:HLA Antigens