HLA Class I and II Blocks Are Associated to Susceptibility, Clinical Subtypes and Autoantibodies in Mexican Systemic Sclerosis (SSc) Patients
| Autor: | Javier Cabiedes-Contreras, Gilberto Vargas-Alarcón, Alfredo Cruz-Lagunas, Joaquín Zúñiga, Neng Yu, Edmond J. Yunis, S. M. Alosco, Pamela Mercado-Velázquez, Tatiana Lebedeva, Carlos A. Núñez-Álvarez, Julio Granados, M. Ohashi, Tatiana S. Rodriguez-Reyna |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
Science Population Black People Genetic admixture Human leukocyte antigen Biology White People Genetic predisposition HLA-DQ beta-Chains Humans Allele education skin and connective tissue diseases Mexico Alleles Autoantibodies Demography Genetics Principal Component Analysis education.field_of_study Scleroderma Systemic Multidisciplinary integumentary system Histocompatibility Antigens Class I Haplotype Histocompatibility Antigens Class II Autoantibody Case-control study Middle Aged Case-Control Studies Immunology Medicine Female Disease Susceptibility DNA Topoisomerases Research Article |
| Zdroj: | PLoS ONE, Vol 10, Iss 5, p e0126727 (2015) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | IntroductionHuman leukocyte antigen (HLA) polymorphism studies in Systemic Sclerosis (SSc) have yielded variable results. These studies need to consider the genetic admixture of the studied population. Here we used our previously reported definition of genetic admixture of Mexicans using HLA class I and II DNA blocks to map genetic susceptibility to develop SSc and its complications.MethodsWe included 159 patients from a cohort of Mexican Mestizo SSc patients. We performed clinical evaluation, obtained SSc-associated antibodies, and determined HLA class I and class II alleles using sequence-based, high-resolution techniques to evaluate the contribution of these genes to SSc susceptibility, their correlation with the clinical and autoantibody profile and the prevalence of Amerindian, Caucasian and African alleles, blocks and haplotypes in this population.ResultsOur study revealed that class I block HLA-C*12:03-B*18:01 was important to map susceptibility to diffuse cutaneous (dc) SSc, HLA-C*07:01-B*08:01 block to map the susceptibility role of HLA-B*08:01 to develop SSc, and the C*07:02-B*39:05 and C*07:02-B*39:06 blocks to map the protective role of C*07:02 in SSc. We also confirmed previous associations of HLA-DRB1*11:04 and -DRB1*01 to susceptibility to develop SSc. Importantly, we mapped the protective role of DQB1*03:01 using three Amerindian blocks. We also found a significant association for the presence of anti-Topoisomerase I antibody with HLA-DQB1*04:02, present in an Amerindian block (DRB1*08:02-DQB1*04:02), and we found several alleles associated to internal organ damage. The admixture estimations revealed a lower proportion of the Amerindian genetic component among SSc patients.ConclusionThis is the first report of the diversity of HLA class I and II alleles and haplotypes Mexican patients with SSc. Our findings suggest that HLA class I and class II genes contribute to the protection and susceptibility to develop SSc and its different clinical presentations as well as different autoantibody profiles in Mexicans. |
| Databáze: | OpenAIRE |
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