Human Leukocyte Antigen Profiles of Latin American Populations: Differential Admixture and Its Potential Impact on Hematopoietic Stem Cell Transplantation
The outcome of hematopoietic stem cell transplantation (HSCT) is shaped by both clinical and genetic factors that determine its success. Genetic factors including human leukocyte antigen (HLA) and non-HLA genetic variants are believed to influence the risk of potentially fatal complications after the transplant. Moreover, ethnicity has been proposed as a factor modifying the risk of graft-versus-host disease. The populations of Latin America are a complex array of different admixture processes with varying degrees of ancestral population proportions that came in different migration waves. This complexity makes the study of genetic risks in this region complicated unless the extent of this variation is thoroughly characterized. In this study we compared the HLA-A and HLA-B allele group profiles for 31 Latin American populations and 61 ancestral populations from Iberia, Italy, Sub-Saharan Africa, and America. Results from population genetics comparisons show a wide variation in the HLA profiles from the Latin American populations that correlate with different admixture proportions. Populations in Latin America seem to be organized in at least three groups with (1) strong Amerindian admixture, (2) strong Caucasian component, and (3) a Caucasian-African gradient. These results imply that genetic risk assessment for HSCT in Latin America has to be adapted for different population subgroups rather than as a pan-Hispanic/Latino analysis. 1. Introduction Hematopoietic stem cell transplantation (HSCT) is a curative therapy used for the treatment of malignant and nonmalignant hematologic diseases, congenital immune deficiencies, solid tumors, and metabolic diseases [1]. Its outcome is shaped not only by clinical factors [2], but also by the genetics of the patient-donor pair [3]. Apart from the normal compatibility defined by the human leukocyte antigen (HLA) system [4, 5], variation in several genetic systems is thought to have an impact on the complications experienced by patients that undergo this procedure [6]. Graft-versus-host disease (GVHD) is a major complication affecting the success of the transplant and the survival of the patients. Despite the fact that most transplants are performed with high levels of compatibility in terms of HLA, a significant proportion of these transplants is affected by GVHD. Apart from clinical factors [7], a genetic component for GVHD other than HLA has been pointed out as responsible for the occurrence of GVHD in 10/10 HLA compatible patient-donor pairs [8, 9]. Moreover, an ethnicity-driven risk of suffering GVHD after HSCT
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