Effect of PTPN22, FAS/FASL, IL2RA and CTLA4 genetic polymorphisms on the risk of developing alopecia areata: A systematic review of the literature and meta-analysis

Abstract

Objectives Genetic association studies on alopecia areata (AA) performed in various populations have shown heterogeneous results. The aim of the current review was to synthesize the results of said studies to estimate the impact of FAS, FASL, PTPN22, CTLA4 and IL2RA gene polymorphisms on AA susceptibility. Design A systematic literature search was conducted in the Medline, Web of Science, Scopus, EMBASE and LILACS databases. Studies published up to June 2020 were included. The results available in the grey literature including the Open Grey and Google Scholar databases were also used. The texts of potentially related studies were screened by individual reviewers. Evidence of publication bias was assessed using the Newcastle-Ottawa scale and the quality of evidence was assessed using the GRADE system. The quantitative synthesis was performed using the fixed effect model. Results Out of 1784 articles, we identified 18 relevant articles for the qualitative synthesis and 16 for the quantitative synthesis. In a study of rs2476601 polymorphism of PTPN22 gene, including 1292 cases and 1832 controls, a correlation was found with the risk of developing AA in the allelic model (OR1.49 [95% C:1.13–1.95]), the heterozygous codominant (OR1.44 [95% CI:1:19–1.76]) and dominant model (OR1.43 [95% CI:1.18–1.73]). No association was found between the presence of FASL, PTPN22, CTLA and IL2RA gene polymorphisms with AA susceptibility. Conclusions The results suggest that the T allele of the single nucleoid polymorphism (SNP) rs2476601 in PTPN22 gene is a risk factor for developing alopecia areata. However, more robust studies defining the ethnic background of the population of origin are required, so that the risk identified in the present study can be validated. Additionally, a greater number of studies is necessary to evaluate the role of the FAS, FASL, PTPN22, CTLA4 and IL2RA genetic variants, given the heterogenous results found in the literature.

Genetic Polymorphism of PTPN22 in Autoimmune Diseases: A Comprehensive Review

“…The T allele of the single nucleoid polymorphism (SNP) rs2476601 in the PTPN22 gene is a risk factor for developing alopecia areata. However, more robust studies defining the ethnic background of the population of origin are required, so that the risk identified in the present study can be validated [75]. The PTPN22 1858T allele of SNP rs2476601 is also reported to be associated with an increased risk of generalized vitiligo [76][77][78]…”

Precision Dermatology: A Review of Molecular Biomarkers and Personalized Therapies

“…The increase in these markers suggest an inflammatory milieu, implicating these factors in the autoimmune attack on hair follicles. A significant correlation between the CTLA-4 rs231726 polymorphism and AA susceptibility has also been found [30], which is indicative of mutations in the development of peripheral tolerance and autoimmunity, as well as a significant correlation between the PTPN22 rs2476601 polymorphism (the most common single-nucleotide polymorphism of the gene) and AA [31]. Such genetic markers can help identify inheritance and at-risk populations, along with the development of targeted therapies, for earlier treatment of hair loss.…”

Impact of vitamin D on ultraviolet-induced photoaging and skin diseases

“…This condition usually begins in children and young adults, though can start at any age despite of the skin tone and gender. Currently, up to 2% of the global population is affected by AA [119] with a higher occurrence rate in females, especially in patients with late-onset disease as of age greater than 50 years [120].…”