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