genetic ancestry component proportions are correlated with hiv disease progression daniela...
TRANSCRIPT
Genetic ancestry component proportions are correlated with
HIV disease progressionDaniela 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
HLA
KIR
Peptide
KIR3DL1/S1 in combination with HLA-Bw480Ille
• Slow progression to AIDS• Slow CD4+ T cell decline
KIR2DL2/S2 in combination with HLA-C180Asn
• Fast decrease of CD4+ T cell counts
Caucasian populations
Mexican mestizos are an admixed popultion with Amerindian, European and African genetic
ancestry components
- Genetic ancestry of 476 individuals was succesfully performed using a previously described panel of 128 AIMs
- 0.594 AMI- 0.38 EUR- 0.026 AFR
Significant effect of AMI and EUR genetic ancestry proportions on CD4+ T cell counts
In general, significant KIR and HLA protective effects were stronger for individuals with higher
EUR ancestry
Putative novel KIR-HLA associations with CD4+ T cell counts were observed only when
stratifying genetic ancestry components
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 socio-demographic factors needs to be further assessed.
ACKNOWLEDGEMENTS
Dr. Gustavo Reyes TeránDr. Santiago Ávila Ríos
CIENI, INER
Blood donorsUCSF, San Francisco, USADouglas Nixon
Thalía GarcíaDaniela GarridoVerónica Quiroz
Humberto Valenzuela
HLA typing
Collaborators
Maribel Soto NavaTania Escamilla
Margarita MatíasClaudia GarcíaDaniela Tapia
Ana Paola CarrancoJuan Blanco
CIENI students
Ramón HernándezEdna RodríguezSilvia del ArenalMario Preciado
Carolina DemeneghiRaymundo González
Israel Molina
Clinical Lab
Zeidy ArenasSandra ZamoraCarolina PérezEduardo López
Berenice Cancino
Administrative staff
Israel MaldonadaEstebán PazPablo César
Informatics staff
Center for Cancer Research, Frederick MD, USA
Carrington, MaryMartin, Maureen
Qi, Ying