EUROPEAN ANCESTRY: A RISK FACTOR FOR SEVERE DENGUE DISEASE. GWAS STUDIES IN CUBAN POPULATION 

Sierra, Beatriz ¹ ; Soares, Pedro ²; Garcia, Gissel ¹; Triska, Peter ²; Perez, Ana B. ¹; Aguirre, Eglys ¹; Sakunthabai; Anavaj ³; Pereira, Luisa ³ ;Guzman, Maria G¹.

1 Institute of Tropical Medicine Pedro Kouri, Havana, Cuba

2 Genetic Diversity Group, IPATIMUP, Porto, Portugal

3 Unité de Génétique Fonctionnelle des Maladies Infectieuses, Pasteur Institut, Paris, France 

Introduction: The proclivity showed by certain populations and ethnic groups to develop severe disease, while others remain asymptomatic, support the impact of human genetic factors on DV disease outcome. Particularly Cuban dengue outbreaks have provided evidence of a reduced risk of Black people for severe dengue disease compared to White people. Objectives: Provide insights on how the genetic ancestry can condition the susceptibility to dengue severe disease, thus facilitating the identification of potential dengue susceptibility/resistance genes

Materials and Methods: We conducted a genome-wide association study of 2.5 million single nucleotide polymorphisms in 274 Cuban individuals during the 2006 dengue epidemic, from two cities, Havana and Guantanamo, from the western and eastern sides of the island, respectively. This screening included DF, DHF and asymptomatic cases, and controls geographically matched. The genomic proportions of European, African, Native American and Asian ancestry were evaluated for all the Cuban groups by using the program ADMIXTURE.

Results: Cuban individuals have a mixed composition, mostly from African and European descent. Different patterns in the mean proportions of ancestry among the studied groups are observed, especially in Havana, with the extremes been displayed by the asymptomatic and hemorrhagic fever groups: 32.8% African, 59.3% European, 5.1% Native American and 2.8 Asian ancestries compared with 9.4%, 81.8%, 8.1% and 0.7%, respectively.

Conclusions: European and Cuban white population, mainly from the western side of the island must share genes that are associated to the susceptibility to dengue severe disease among individuals genetically Europeans .