Alopecia areata (AA) is an autoimmune disease that produces non-scarring hair loss through the body at any age.1 AA is commonly presented as single or multiple rounded patches, although complete baldness may occur, which is called AA totalis. If the hair loss occurs throughout the body is known as AA universalis. AA can also be presented as in the circumference of the head and is known as AA ophis.2 AA is considered a polygenic disease influenced by a genetically complex inheritance, especially of autoimmune and inflammatory related genes, along with environmental factors.3,4 Various genes of the immune system have been reported to contribute to the development of this disease, such as the autoimmune regulator (AIRE) gene, human leukocyte antigen (HLA), interleukin (IL) genes, cytotoxic T lymphocyte-associated antigen 4 (CTLA4), protein tyrosine phosphatase non-receptor type 22 (PTPN22), tumor necrosis factor superfamily member 6 or CD95 (FAS) and FAS ligand (FASL) among others.5,6

The cytotoxic T-lymphocyte antigen 4 (CTLA4) gene (2q34) is a member of the immunoglobulin superfamily encoding a protein whose function is that of a potent negative regulator of T-cell response. Also involved in the maintenance of immune tolerance, it has been implicated as a susceptibility gene in human autoimmune diseases, presenting several polymorphisms that have been associated with its development.7 Among the latter, two genetic variants may contribute to AA susceptibility: +49AG (rs231775), a missense variation leading to a threonine to alanine aminoacid substitution at codon 17 in the leader peptide (T17A); and CT60 (rs3087243), located 236 bp downstream of CTLA4 gene (3′-UTR).8 However, recent studies conducted in different populations have shown that the relationship of these genetic variants in the development of AA is controversial.3,9

The current study sought to determine whether the CTLA4 +49AG (rs231775) and CT60 (rs3087243) gene variants constitute a predisposition factor for AA in a cohort of Mexican patients.

AA is an autoimmune hair-loss condition that has been associated with multiple gene variants, several of which participate in immune response pathways related to HLA.12 The CTLA4 gene product is a receptor expressed by CD4+ and CD8+ T-cells. Experiments in knockout mice have demonstrated the important role that CTLA4 plays in protection against autoimmunity. CTLA-4 is a critical negative regulator of T cell responses, and the action of CTLA4 on Treg cells can control the activity of other cells and controlling fatal autoimmunity.13

The association between the presence of the CTLA4 gene variants and the development of different autoimmune diseases has been suggested.14,15 However in immune dermatological diseases, the results have been controversial; in vitiligo their participation or lack of influence16 has been seen. A similar situation has been observed with the development of psoriasis.17,18

In this regard, considering the possible contribution of the autoimmune function in alopecia, genetic variant studies of CTLA4 gene have been explored in diverse populations. A previous association analysis has suggested the plausible involvement of CTLA4 gene variants as a risk factor in the development of AA in a European population,8 with a stronger effect in patients with severe forms of the disorder.

Another study conducted on an Italian population, where rs231775 and rs3087243 gene variants were analyzed, observed the latter as a risk factor in the development of patchy AA.9 On the other hand, a study conducted on Iran nationals failed to prove the association of the rs3087243 gene variant in the development of AA.3

Previously, we observed the participation of genetic variants of TNFα and PTPN2219 as a risk factor for AA in Mexican patients; both of these genes’ function is related to the regulation of immune mechanisms. However, the participation of CTLA4 genetic variants in AA has not been analyzed in this population.

Some SNPs within the CTLA-4 gene have already been analyzed for susceptibility to rheumatoid arthritis (RA) in the Mexican population; among them, rs5742909, rs231775 and rs3087243, suggesting that the −319C/+49G/CT60G haplotype of the CTLA-4 gene is a risk factor for RA, whereas that the rs3087243 SNP could be a protective factor against this type of autoimmune disease.20

However, no significant differences were observed for rs231775 and rs3087243 in our study population (Table 2), suggesting that these variants are not a risk factor in the development of AA or Patchy AA in the Mexican population.

In conclusion, the genetic variants rs231775 and rs3087243 of the CTLA4 gene do not constitute a risk factor in the development of AA in the Mexican population of Monterrey, Mexico. Further, these genetic variants have no association between family/personal backgrounds of autoimmune diseases or the gender of the study subjects.

None declared.

Mauricio Andrés Salinas Santander: Statistic analysis; approval of the final version of the manuscript; conception and planning of the study; elaboration and writing of the manuscript; obtaining, analysis, and interpretation of the data; effective participation in research orientation; critical review of the literature; critical review of the manuscript.

Cristina Susana Cantu-Salinas: Approval of the final version of the manuscript; conception and planning of the study; elaboration and writing of the manuscript; obtaining, analysis, and interpretation of the data; effective participation in research orientation; critical review of the literature; critical review of the manuscript.

Jorge Ocampo-Candiani: Approval of the final version of the manuscript; conception and planning of the study; effective participation in research orientation; critical review of the literature; critical review of the manuscript.

Victor de Jesus Suarez-Valencia: Approval of the final version of the manuscript; elaboration and writing of the manuscript; obtaining, analysis, and interpretation of the data; critical review of the literature; critical review of the manuscript.

Jennifer Guadalupe Ramirez-Guerrero: Approval of the final version of the manuscript; elaboration and writing of the manuscript; obtaining, analysis, and interpretation of the data; critical review of the literature.

Celia Nohemi Sanchez-Dominguez: Approval of the final version of the manuscript; elaboration and writing of the manuscript; critical review of the literature; critical review of the manuscript.

None declared.