Heterogeneity of Genetic Admixture Determines SLE Susceptibility in Mexican
Systemic Lupus Erythematosus (SLE) is an autoimmune inflammatory disorder for which Major Histocompatibility Complex (MHC) genes are well identified as risk factors. SLE patients present different clinical phenotypes, which are partly explained by admixture patterns variation among Mexicans. Populat...
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Format: | Article |
Language: | English |
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Frontiers Media S.A.
2021-08-01
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Series: | Frontiers in Genetics |
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Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2021.701373/full |
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doaj-6af9f3c697f341268049bbd6bee001e2 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Susana Hernández-Doño Juan Jakez-Ocampo José Eduardo Márquez-García Daniela Ruiz Víctor Acuña-Alonzo Guadalupe Lima Luis Llorente Víctor Hugo Tovar-Méndez Rafael García-Silva Julio Granados Joaquín Zúñiga Joaquín Zúñiga Gilberto Vargas-Alarcón |
spellingShingle |
Susana Hernández-Doño Juan Jakez-Ocampo José Eduardo Márquez-García Daniela Ruiz Víctor Acuña-Alonzo Guadalupe Lima Luis Llorente Víctor Hugo Tovar-Méndez Rafael García-Silva Julio Granados Joaquín Zúñiga Joaquín Zúñiga Gilberto Vargas-Alarcón Heterogeneity of Genetic Admixture Determines SLE Susceptibility in Mexican Frontiers in Genetics HLA Mexican population genetics heterogeneity HLA-DRB1∗03:01 admixture |
author_facet |
Susana Hernández-Doño Juan Jakez-Ocampo José Eduardo Márquez-García Daniela Ruiz Víctor Acuña-Alonzo Guadalupe Lima Luis Llorente Víctor Hugo Tovar-Méndez Rafael García-Silva Julio Granados Joaquín Zúñiga Joaquín Zúñiga Gilberto Vargas-Alarcón |
author_sort |
Susana Hernández-Doño |
title |
Heterogeneity of Genetic Admixture Determines SLE Susceptibility in Mexican |
title_short |
Heterogeneity of Genetic Admixture Determines SLE Susceptibility in Mexican |
title_full |
Heterogeneity of Genetic Admixture Determines SLE Susceptibility in Mexican |
title_fullStr |
Heterogeneity of Genetic Admixture Determines SLE Susceptibility in Mexican |
title_full_unstemmed |
Heterogeneity of Genetic Admixture Determines SLE Susceptibility in Mexican |
title_sort |
heterogeneity of genetic admixture determines sle susceptibility in mexican |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Genetics |
issn |
1664-8021 |
publishDate |
2021-08-01 |
description |
Systemic Lupus Erythematosus (SLE) is an autoimmune inflammatory disorder for which Major Histocompatibility Complex (MHC) genes are well identified as risk factors. SLE patients present different clinical phenotypes, which are partly explained by admixture patterns variation among Mexicans. Population genetic has insight into the high genetic variability of Mexicans, mainly described through HLA gene studies with anthropological and biomedical importance. A prospective, case-control study was performed. In this study, we recruited 146 SLE patients, and 234 healthy individuals were included as a control group; both groups were admixed Mexicans from Mexico City. The HLA typing methods were based on Next Generation Sequencing and Sequence-Based Typing (SBT). The data analysis was performed with population genetic programs and statistical packages. The admixture estimations based on HLA-B and -DRB1 revealed that SLE patients have a higher Southwestern European ancestry proportion (48 ± 8%) than healthy individuals (30 ± 7%). In contrast, Mexican Native American components are diminished in SLE patients (44 ± 1%) and augmented in Healthy individuals (63 ± 4%). HLA alleles and haplotypes’ frequency analysis found variants previously described in SLE patients from Mexico City. Moreover, a conserved extended haplotype that confers risk to develop SLE was found, the HLA-A∗29:02∼C∗16:01∼B∗44:03∼DRB1∗07:01∼DQB1∗02:02, pC = 0.02, OR = 1.41. Consistent with the admixture estimations, the origin of all risk alleles and haplotypes found in this study are European, while the protection alleles are Mexican Native American. The analysis of genetic distances supported that the SLE patient group is closer to the Southwestern European parental populace and farthest from Mexican Native Americans than healthy individuals. Heterogeneity of genetic admixture determines SLE susceptibility and protection in Mexicans. HLA sequencing is helpful to determine susceptibility alleles and haplotypes restricted to some populations. |
topic |
HLA Mexican population genetics heterogeneity HLA-DRB1∗03:01 admixture |
url |
https://www.frontiersin.org/articles/10.3389/fgene.2021.701373/full |
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doaj-6af9f3c697f341268049bbd6bee001e22021-08-03T08:36:20ZengFrontiers Media S.A.Frontiers in Genetics1664-80212021-08-011210.3389/fgene.2021.701373701373Heterogeneity of Genetic Admixture Determines SLE Susceptibility in MexicanSusana Hernández-Doño0Juan Jakez-Ocampo1José Eduardo Márquez-García2Daniela Ruiz3Víctor Acuña-Alonzo4Guadalupe Lima5Luis Llorente6Víctor Hugo Tovar-Méndez7Rafael García-Silva8Julio Granados9Joaquín Zúñiga10Joaquín Zúñiga11Gilberto Vargas-Alarcón12Immunogenetics Division, Department of Transplant, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, MexicoDepartment of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, MexicoMolecular Biology Core Facility, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, MexicoDepartment of Dermatology, Hospital General Dr. Manuel Gea González, Mexico City, MexicoLaboratory of Physiology, Biochemistry, and Genetics, Escuela Nacional de Antropología e Historia, Mexico City, MexicoDepartment of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, MexicoDepartment of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, MexicoDepartment of Endocrinology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, MexicoDepartment of Internal Medicine, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, MexicoImmunogenetics Division, Department of Transplant, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, MexicoLaboratory of Immunobiology and Genetics, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, MexicoTecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Mexico City, Mexico0Research Direction, Instituto Nacional de Cardiología Ignacio Chavez, Mexico City, MexicoSystemic Lupus Erythematosus (SLE) is an autoimmune inflammatory disorder for which Major Histocompatibility Complex (MHC) genes are well identified as risk factors. SLE patients present different clinical phenotypes, which are partly explained by admixture patterns variation among Mexicans. Population genetic has insight into the high genetic variability of Mexicans, mainly described through HLA gene studies with anthropological and biomedical importance. A prospective, case-control study was performed. In this study, we recruited 146 SLE patients, and 234 healthy individuals were included as a control group; both groups were admixed Mexicans from Mexico City. The HLA typing methods were based on Next Generation Sequencing and Sequence-Based Typing (SBT). The data analysis was performed with population genetic programs and statistical packages. The admixture estimations based on HLA-B and -DRB1 revealed that SLE patients have a higher Southwestern European ancestry proportion (48 ± 8%) than healthy individuals (30 ± 7%). In contrast, Mexican Native American components are diminished in SLE patients (44 ± 1%) and augmented in Healthy individuals (63 ± 4%). HLA alleles and haplotypes’ frequency analysis found variants previously described in SLE patients from Mexico City. Moreover, a conserved extended haplotype that confers risk to develop SLE was found, the HLA-A∗29:02∼C∗16:01∼B∗44:03∼DRB1∗07:01∼DQB1∗02:02, pC = 0.02, OR = 1.41. Consistent with the admixture estimations, the origin of all risk alleles and haplotypes found in this study are European, while the protection alleles are Mexican Native American. The analysis of genetic distances supported that the SLE patient group is closer to the Southwestern European parental populace and farthest from Mexican Native Americans than healthy individuals. Heterogeneity of genetic admixture determines SLE susceptibility and protection in Mexicans. HLA sequencing is helpful to determine susceptibility alleles and haplotypes restricted to some populations.https://www.frontiersin.org/articles/10.3389/fgene.2021.701373/fullHLAMexicanpopulation geneticsheterogeneityHLA-DRB1∗03:01admixture |