Human Leukocyte Antigen-DRB1 Class II Genes in Mexican Amerindian Mazahuas: Genes and Languages Do Not Correlate Antonio Arnaiz-Villena, 1 Sedeka Abd-El-Fatah, 2 Marı ´a Angeles Granados-Silvestre, 3 Carlos Parga-Lozano, 1 Pablo Go ´ mez-Prieto, 1 Diego Rey, 1 Cristina Areces, 1 Patricia Pen ˜ aranda, 2 Martha Menjı ´var, 3 Jose ´ Manuel Rodrı ´guez-Pe ´ rez, 4 Julio Granados, 5 and Gilberto Vargas-Alarco ´n 4 Background: The major histocompatibility complex genes are located on the short arm of the human sixth chro- mosome; they are highly polymorphic and therefore have been very advantageous in population genetic studies. Methods: A Mazahua group established in North Mexico State and also in nearby Michoacan state in the rainy mountain highlands (Mexico) was studied for their human leukocyte antigen (HLA)-DRB1 alleles. The relationship with other Amerindians and worldwide populations was studied by using 14,996 chromosomes from 75 different populations and calculating neighbor-joining dendrograms and correspondence multidimensional values. Results: Five principal HLA allele frequencies were found in our group: DRB1*0802 (the most frequent one in this pop- ulation), DRB1*0407, DRB1*0403, DRB1*0101, and DRB1*1406. Both genetic distances and correspondence analyses clearly show that our Mazahua group is genetically close to some of the most ancient groups living in Mexico (Mayos, Zapotecans, Tennek) and South American Amerindians. Amerindians remain as a group apart from the rest of the world. Conclusions: The results analyzing the HLA-DR locus suggest that Mazahua language (Oto- mangue) does not correlate with those of the most closely HLA-correlated ethnic groups. The present data may be useful for future transplantation programs, HLA and disease diagnosis, and pharmacogenetic studies. Introduction M azahua Amerindian groups live today in the rainy and wild mountains of Mexico and in the Michoacan States in Mexico. They speak Mazahua, which belongs to the Otomangue group (Scheffler, 1992). Some historians relate Mazahuas with northern desert groups that migrated south- wards during the VI–XIII centuries AD and belong to part of the Chichimecan ethnic group; Mazahuas joined with Spanish invaders against the Mexican Empire after 1521 AD (http:// ignorantisimo.free.fr/CELA/docs/Mazahuas.pdf ). They have also migrated to many other parts of Mexico. In the present work, we aim to study the human leukocyte antigen (HLA)-DRB1 profile of Mazahuas-speaking people from North Mexico State and also from nearby Michoacan State in the rainy and cool mountains ( Mexico). We also aim to relate this profile with other Amerindians and worldwide populations in order to establish degrees of genetic related- ness with different populations. Materials and Methods Population sampling We studied 65 healthy unrelated volunteers from a Ma- zahua ethnic group living in a little relatively isolated vil- lage, Jaltepec, close to San Felipe del Progreso (Mexico State) (Fig. 1). Each individual had a Mexican Amerindian physical appearance and their four grandparents were born in the same area and spoke Mazahua. The present study was ap- proved by the Bioethics and Research Committee from the Instituto Nacional de Cardiologı ´a and all study subjects voluntarily signed an informed consent letter. The origin of all other populations used for comparisons are detailed in Figure 2. A total of 14,996 chromosomes were studied, in- cluding populations from different origins (Caucasoids, Orientals, Negroids, Polynesians, Micronesians, Na-Dene, Eskimos, and Amerindians). In particular, the Amerindian group includes groups belonging to the following linguis- tic families: Macro-Mixteco (Mixtecans, Zapotecans, and 1 Department of Immunology, University Complutense, The Madrid Regional Blood Center, Madrid, Spain. 2 Department of Hematology, The Madrid Regional Blood Center, Madrid, Spain. 3 Facultad de Quı ´mica, Departamento de Biologı ´a, Universidad Nacional Auto ´noma de Me ´xico, Mexico City, Mexico. 4 Department of Molecular Biology, Instituto Nacional de Cardiologı ´a Ignacio Cha ´vez. Mexico City, Mexico. 5 Immunogenetics Division, Transplantation Department, Instituto Nacional de Ciencias Me ´dicas y Nutricio ´ n Salvador Zubiran, Mexico City, Mexico. GENETIC TESTING AND MOLECULAR BIOMARKERS Volume 15, Number 1-2, 2011 ª Mary Ann Liebert, Inc. Pp. 97–102 DOI: 10.1089/gtmb.2010.0055 97