CTLA4 +49AG (rs231775) and CT60 (rs3087243) gene variants are not associated with alopecia areata in a Mexican population from Monterrey Mexico.

BACKGROUND: Alopecia areata is an autoimmune disease that produces non-scarring hair loss around the body. Gene variants of the cytotoxic T-lymphocyte antigen 4 (CTLA4) gene, a negative regulator of T-cell response, have been associated with a predisposition to autoimmune diseases in different populations; however, the involvement of these genetic variants in the development of AA is controversial. OBJECTIVE: The present study evaluated the potential association of two CTLA4 gene variants with alopecia areata in a Mexican population. METHODS: We genotyped +49AG (rs231775) and CT60 (rs3087243) variants in 50 AA patients and 100 healthy control participants through PCR-RFLP. RESULTS: No statistical difference was observed for either of the gene variants regarding allele or genotype frequencies between AA patients and the controls when the parameters of family/personal history of autoimmune diseases or gender were considered (p>0.05). STUDY LIMITATIONS: Small sample size of patients and the data were obtained from Northeast Mexico population. CONCLUSION: The genetic variants rs231775 and rs3087243 of the CTLA4 gene are not a risk factor for the development of alopecia areata in the analyzed Mexican population.

CAPN3, DCT, MLANA and TYRP1 are overexpressed in skin of vitiligo vulgaris Mexican patients.

Vitiligo is a disorder causing skin depigmentation, in which several factors have been proposed for its pathogenesis: Environmental, genetic and biological aspects of melanocytes, even those of the surrounding keratinocytes. However, the lack of understanding of the mechanisms has complicated the task of predicting the development and progression. The present study used microarray analysis to characterize the transcriptional profile of skin from Vitiligo Vulgaris (VV) patients and the identified transcripts were validated using targeted high-throughput RNA sequencing in a broader set of patients. For microarrays, mRNA was taken from 20 skin biopsies of 10 patients with VV (pigmented and depigmented skin biopsy of each), and 5 biopsies of healthy subjects matched for age and sex were used as a control. A signature was identified that contains the expression pattern of 722 genes between depigmented vitiligo skin vs. healthy control, 1,108 between the pigmented skin of vitiligo vs. healthy controls and 1,927 between pigmented skin, depigmented vitiligo and healthy controls (P<0.05; false discovery rate, <0.1). When comparing the pigmented and depigmented skin of patients with vitiligo, which reflects the real difference between both skin types, 5 differentially expressed genes were identified and further validated in 45 additional VV patients by RNA sequencing. This analysis showed significantly higher RNA levels of calpain-3, dopachrome tautomerase, melan-A and tyrosinase-related protein-1 genes. The data revealed that the pigmented skin of vitiligo is already affected at the level of gene expression and that the main differences between pigmented and non-pigmented skin are explained by the expression of genes associated with pigment metabolism.

Association between PTPN22 C1858T polymorphism and alopecia areata risk.

Alopecia areata (AA) is a skin condition in which hair is lost from certain or all areas of the body. This condition has been described as an immune-mediated complex genetic disease, characterized by the presence of lymphocytes that are directed to the hair follicles in the anagen phase. The gene encoding the protein tyrosine phosphatase, non-receptor type 22 (PTPN22), which is exclusively expressed in immune cells, has been considered as a risk factor associated with a number of autoimmune diseases. In AA, the single nucleotide polymorphism, rs2476601, has been identified as a risk factor in several populations. The aim of the present study was to investigate the effect of PTPN22 C1858T inherited genetic polymorphism on the predisposition to severe forms of AA, in a case-control study on individuals. The study included 64 unrelated patients diagnosed with several types of AA, as well as 225 healthy unrelated subjects. The DNA samples were genotyped for PTPN22 C1858T polymorphism using the polymerase chain reaction-restriction fragment length polymorphism technique. Causal associations were determined by χ2 test and their respective odds ratio (OR) was assessed in a 2×2 contingency table. The results demonstrated a significant association of the T allele [P=0.040; OR=3.196; 95% confidence interval (CI), 0.094-10.279] and the CT genotype (P=0.038; OR=3.313; 95% CI, 1.008-10.892) with patchy AA. In conclusion, the results of the present study suggested the possible involvement of the T allele of the PTPN22 C1858T SNP as a genetic risk factor for this type of AA in the population studied.

Tumor necrosis factor-α -308G/A polymorphism is associated with active vitiligo vulgaris in a northeastern Mexican population.

Vitiligo is a skin disease characterized by depigmentation. Its etiopathogenesis is unclear, but it has been associated with autoimmune processes. Gene polymorphisms in the tumor necrosis factor-α (TNF-α) have been associated with several imflammatory diseases. In particular, the -308G/A polymorphism in the gene promoter region has been reported to be associated with increased plasma levels of TNF-α and with an increased risk to develop autoimmune diseases. To date, this polymorphism has not been associated with vitiligo. To assess a possible association between the TNF-α -308G/A and vitiligo vulgaris (VV), 198 vitiligo patients and 395 control subjects were recruited for the study. A complete demographic and clinical profile of each case was registered to analyze the possible risk factors of vitiligo. Genomic DNA isolated from peri pheral blood was subjected to PCR-RFLP for genotyping of the TNF-α -308G/A polymorphism. Causal associations were determined by χ(2) test and their respective OR was assessed in a 2×2 contingency table. When population variables of type of vitiligo, gender, age of disease onset, and active disease status were considered, an association between active VV and the TNF-α GA genotype was found (P=0.0295, OR=2.0; 95% CI 1.01-3.93). All other variables were irrelevant to vitiligo. Our data suggest a possible association between the TNF-α -308 GA genotype and the active form of VV in a Mexican population.