ABSTRACT
BACKGROUND: Psoriasis is an autoimmune-related chronic inflammatory skin disorder. Psoriasis vulgaris (PV) is the most common form of psoriasis. T regulatory cells (Tregs) are typically considered inhibitors of autoimmune responses. FOXP3 is a master control transcription factor for development and function of Tregs. FOXP3 gene polymorphism changes FOXP3 protein function and quantity leading to Tregs dysfunction that subsequently may be related to PV pathogenesis. OBJECTIVE: The objective of the present study was to evaluate the possible role of FOXP3 gene (rs3761548) polymorphism in PV pathogenesis. MATERIALS AND METHODS: One hundred sixty subjects were included in the present study (80 PV patients and 80 well-matched healthy controls). All participants were evaluated by detailed history, general examination, dermatological examination, and psoriasis area and severity index (PASI) score. The detection of FOXP3 gene (rs3761548) polymorphism in patients and controls by PCR-restriction fragment length polymorphism technique was done. RESULTS: There was statistically significant increase in CC genotype and C allele in patients compared to controls, whereas there were non-significant differences in AA and AC genotypes. However, there were non-significant associations between genotype distribution and each of age, sex, family history, PASI score, hair affection, nail affection, hypertension, diabetes mellitus, and body mass index. CONCLUSION: FOXP3 gene (rs3761548) polymorphism may increase susceptibility of PV and share in its pathogenesis as it leads to changes in FOXP3 protein function and quantity that subsequently affect T-regs functions. Further investigations for the role of other FOXP3 genes polymorphisms in psoriasis pathogenesis and their effects on the treatment response in psoriasis patients are strongly recommended.
ABSTRACT
Psoriasis is a chronic inflammatory disorder of the skin, with genetic factors reportedly involved in the disease pathogenesis. Numerous studies reported psoriasis candidate genes. However, these tend to involve mostly in the European and Asian populations. Here, we report the first genome-wide association study (GWAS) in an Egyptian population, identifying susceptibility variants for psoriasis using a two-stage case-control design. In the first discovery stage, we carried out a genome-wide association analysis using the Infinium® Global Screening Array-24 v1.0, on 253 cases and 449 control samples of Egyptian descent. In the second replication stage, 26 single-nucleotide polymorphisms (SNPs) were selected for replication in additional 321 cases and 253 controls. In concordance with the findings from previous studies on other populations, we found a genome-wide significant association between the MHC locus and the disease at rs12199223 (Pcomb = 6.57 × 10-18 ) and rs1265181 (Pcomb = 1.03 × 10-10 ). Additionally, we identified a novel significant association with the disease at locus, 4q32.1 (rs12650590, Pcomb = 4.49 × 10-08 ) in the vicinity of gene GUCY1A3, and multiple suggestive associations, for example rs10832027 (Pcomb = 7.28 × 10-06 ) and rs3770019 (Pcomb = 1.02 × 10-05 ). This proposes the existence of important interethnic genetic differences in psoriasis susceptibility. Further studies are necessary to elucidate the downstream pathways of the new candidate loci.
Subject(s)
Genetic Predisposition to Disease , Polymorphism, Single Nucleotide , Psoriasis/genetics , Case-Control Studies , Egypt/epidemiology , Female , Genome, Human , Genome-Wide Association Study , Genotype , Humans , Inflammation , Major Histocompatibility Complex , Male , Oligonucleotide Array Sequence Analysis , RiskABSTRACT
PROBLEM: Little is known about how preeclampsia affects regulatory T-cell count and functions in umbilical cord blood of babies born to preeclamptic mothers. Here, we analyze the percentage of CD4+ CD25high FOXP3+ , CD4+ CD25low FOXP3+ , and CD4+ FOXP3+ Tregs, in the umbilical cord blood of babies born to mothers with and without preeclampsia. METHOD OF STUDY: The percentage of umbilical cord blood CD4+ CD25high FOXP3+ , CD4+ CD25low FOXP3+ , and CD4+ FOXP3+ Tregs were analyzed by flow cytometry. RESULTS: CD4+ CD25high FOXP3+ Treg (%) and CD4+ FOXP3+ Treg (%) were significantly lower, while CD4+ CD25low (%) was significantly higher in umbilical cord blood of babies born to preeclamptic mothers. CONCLUSION: Preeclampsia is associated with immune dysregulation which leads to a deficiency in Treg (CD4+ CD25high FOXP3+ ) in the umbilical cord blood of babies born to preeclamptic mothers.
