Human leukocyte antigen profiles of latin american populations: differential admixture and its potential impact on hematopoietic stem cell transplantation

Abstract

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.

Figure 1

Map showing the approximate location of the LAP included in the study.

Figure 2

Cluster analysis based on 47 HLA-A and HLA-B allele group frequencies among 31 LAP and 61 ancestral populations. (a) Dendrogram showing the clustering of the 92 populations. (b) Dendrogram showing the dual-clustering of HLA allele groups in the dataset. SSA: Sub-Saharan Africans; SAL: South American Lowlanders; SAA: South American Andeans; CA: Central Americans; NAA: North Americans and Alaskans; SAf: Southern Africans; EAf, Eastern Africans; CAf: Central Africans; WAf: Western Africans; Spm: Spanish minorities; Sp: Spanish; BC: Brazilians and Cubans; PIA: Portuguese, Italians, and Argentinians; NLA: Northern Latin Americans.

Figure 3

Principal coordinates analysis (PCO) based on the frequencies of 47 HLA-A and HLA-B allele groups in 31 LAP and 61 ancestral populations. (a) PCO map of the first 2 principal components (57.7% cumulative variance) for 61 ancestral populations from sub-Saharan Africa (SSA), America, and Europe. (b) PCO map showing the first 2 principal components (56.7% cumulative variance) for 31 LAP (blue) and 61 ancestral populations.

Figure 4

Frequency of ethnic-specific HLA allele groups among three subgroups of LAP and the ancestral populations. (a) Frequency of HLA-A*25 allele group as a Caucasian marker. (b) Frequency of HLA-B*42 allele group as a Sub-Saharan African (SSA) marker. (c) Frequency of HLA-B*48 as an Amerindian marker.