Slides
Genetic ancestry component proportions are correlated with HIV disease progression Daniela Garrido-Rodríguez, Santiago Ávila-Ríos, Humberto Valenzuela-Ponce, Thalía A. García-Téllez, Veronica Quiroz-Morales, Claudia García-Morales, Maribel Soto-Nava, Akio Murakami-Ogasawara, Juan Carlos Fernandez-Lopez, Gustavo Reyes-Terán Several genetic factors are associated to HIV disease outcome KIR KIR3DL1/S1 in combination with HLA-Bw480Ille • Slow progression to AIDS • Slow CD4+ T cell decline HLA KIR2DL2/S2 in combination with HLA-C180Asn • Fast decrease of CD4+ T cell counts Peptide Caucasian populations Mexican mestizos are an admixed popultion with Amerindian, European and African genetic ancestry components - 0.594 AMI - 0.38 EUR - 0.026 AFR - Genetic ancestry of 476 individuals was succesfully performed using a previously described panel of 128 AIMs Significant effect of AMI and EUR genetic ancestry proportions on CD4+ T cell counts EUR NAT 1.0 1.0 0.8 r=0.04004 p=0.3835 0.6 0.4 r=-0.01508 p=0.7427 0.2 0.0 Ancestry proportions Ancestry proportions 0.8 0.6 r= -0.1311 p=0.0043 r=0.1361 p=0.0030 0.4 0.2 2 3 4 5 pVL Setpoint (RNA copies/ml) 6 0.0 500 1000 CD4+ T cell count (cells/ml) 1500 Putative novel KIR-HLAKIR associations with CD4+ In general, significant and HLA protective T cell counts were only when effects were stronger forobserved individuals with higher stratifying genetic ancestry components EUR ancestry Conclusions • Genetic stratification within a population is important when assessing the effect of genetic factors on HIV disease outcome. • Differential effects of specific genetic factors observed in individuals with distinct genetic ancestry components in admixed populations. • HLA and KIR effects can partially explain differences observed in pVL setpoint and CD4+ T cell counts in individuals with different genetic ancestry components. • The possible effect of other genetic factors as well as sociodemographic factors needs to be further assessed. ACKNOWLEDGEMENTS HLA typing Thalía García Daniela Garrido Verónica Quiroz Humberto Valenzuela Collaborators Maribel Soto Nava Tania Escamilla Margarita Matías Claudia García Daniela Tapia Ana Paola Carranco Juan Blanco CIENI students Clinical Lab Ramón Hernández Edna Rodríguez Silvia del Arenal Mario Preciado Carolina Demeneghi Raymundo González Israel Molina CIENI, INER Dr. Gustavo Reyes Terán Dr. Santiago Ávila Ríos UCSF, San Francisco, USA Douglas Nixon Center for Cancer Research, Frederick MD, USA Carrington, Mary Martin, Maureen Qi, Ying Administrative staff Zeidy Arenas Sandra Zamora Carolina Pérez Eduardo López Berenice Cancino Informatics staff Israel Maldonada Estebán Paz Pablo César Blood donors
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