Genome-wide association study in alopecia areata implicates both innate and adaptive immunity

Petukhova, Lynn; Duvic, Madeleine; Hordinsky, Maria; Norris, David A.; Price, Vera H.; Shimomura, Yutaka; Kim, Hyun-Mi; Singh, Pallavi; Lee, Annette; Chen, Wei V.; Meyer, Katja; Paus, Ralf; Jahoda, Colin A.B.; Amos, Christopher I.; Gregersen, Peter K.; Christiano, Angela M.

doi:10.1038/nature09114

Cited by 678 publications

(703 citation statements)

References 38 publications

Supporting

Mentioning

647

Contrasting

Unclassified

Order By: Relevance

“…Indeed, focal T lymphocytes infiltration [4] and deposition of hair folliclespecific autoantibodies [5] are present in anagen stage (growing) hair follicles. Susceptibility to AA has been referred to a polygenic complex [6,7] comprising immune system genes coding for the human leukocyte antigens (HLA) or other immune-related gene products [8,9].…”

Section: Introductionmentioning

confidence: 99%

Single nucleotide polymorphisms in the promoter regions of Foxp3 and ICOSLG genes are associated with Alopecia Areata

et al. 2012

View full text Add to dashboard Cite

Alopecia areata (AA), an autoimmune disease affecting anagen stage hair follicles, is associated with polymorphisms in immune-related genes and with decreased number of CD4? CD25? T regulatory cells (Treg). Treg function is modulated by the forkhead box protein 3 (FOXP3) transcription factor and by inducible costimulator (ICOS), through interaction with the relative ligand, ICOSLG, whose genes are polymorphic. The aim of the study was to investigate whether specific single nucleotide polymorphisms (SNPs) of the rs2294020 FOXP3 and/ or rs378299 ICOSLG genes may be associated with AA. A case-control study was performed in 120 AA patients and 84 controls. SNPs were analyzed by gene sequencing. FOXP3 and ICOSLG gene expressions were analyzed by real-time PCR. Increased frequencies of the genotype carrying the FOXP3 rs2294020-3675(A) [P = 0.002, OR (95 % CI): 2.55 (1.2-2.7)] or the ICOSLG rs378299-509(C) [P = 0.01, OR (95 % CI): 2.21 (1.1-2.6)] allelic variants were observed in AA patients than in controls. The genotype carrying the combination of the FOXP3 rs2294020-3675(A) and ICOSLG rs378299-509(C) allelic variants with the HLA DQB1*03 allele was more frequently present in AA patients than in controls (P = 0.04). The presence of the FOXP3 rs2294020-3675(A) or the I-COSLG rs378299-509(C) allelic variant was associated with reduced relative gene expression in AA patients. These data suggest that rs2294020 SNP of FOXP3 gene and rs378299 SNP of ICOSLG gene are associated with AA and with a reduced expression of the FOXP3 and ICOSLG genes in alopecia patients.

show abstract

Section: Introductionmentioning

confidence: 99%

Single nucleotide polymorphisms in the promoter regions of Foxp3 and ICOSLG genes are associated with Alopecia Areata

et al. 2012

View full text Add to dashboard Cite

show abstract

“…This weak association is in line with the findings of a GWAS conducted in a Caucasian population. 126 The association between PTPN22 C1858T and primary Sjogren's syndrome (pSS) is not clear. One study from Columbia (70 cases and 308 controls) identified a strong association (OR ¼ 2.42; 95% CI ¼ 1.23-4.75, P ¼ 0.01); this was similar to that for SLE, but stronger than that for RA or T1D in the same population.…”

Section: Diseases Showing No or Weak Association With Ptpn22mentioning

confidence: 99%

Meta-analysis reveals an association of PTPN22 C1858T with autoimmune diseases, which depends on the localization of the affected tissue

et al. 2012

View full text Add to dashboard Cite

Protein tyrosine phosphatase non-receptor type 22 (PTPN22) is a strong susceptibility gene shared by many autoimmune diseases. The aim of this study was to explore the mechanisms underlying this relationship. We performed a comprehensive analysis of the association between PTPN22 polymorphism C1858T and autoimmune diseases. The results showed a remarkable pattern; PTPN22 C1858T was strongly associated with type I diabetes, rheumatoid arthritis, immune thrombocytopenia, generalized vitiligo with concomitant autoimmune diseases, idiopathic inflammatory myopathies, Graves' disease, juvenile idiopathic arthritis, myasthenia gravis, systemic lupus erythematosus, anti-neutrophil cytoplasmic antibody-associated vasculitis and Addison's disease. By contrast, PTPN22 C1858T showed a negligible association with systemic sclerosis, celiac disease, multiple sclerosis, psoriasis, ankylosing spondylitis, pemphigus vulgaris, ulcerative colitis, primary sclerosing cholangitis, primary biliary cirrhosis, Crohn's disease and acute anterior uveitis. Further analysis revealed a clear distinction between the two groups of diseases with regard to their targeted tissues: most autoimmune diseases showing an insignificant association with PTPN22 C1858T manifest in skin, the gastrointestinal tract or in immune privileged sites. These results showed that the association of PTPN22 polymorphism with autoimmune diseases depends on the localization of the affected tissue, suggesting a role of targeted organ variation in the disease manifestations.

show abstract

“…These polymorphisms (IL2/IL21, IL2RA, CTLA4, IK2F4, HLA, NK-activating ligands, ILBP6, ULBP6, STX17, PRDX5) were found be associated with T cells or the hair follicle. In addition, there was a region of strong association on the cytomegalovirus UL16-Binding Protein Gene Cluster (ULBP) [9]. This gene cluster encodes the activating ligands of natural killer cell receptor NKG2D.…”

Section: Geneticsmentioning

confidence: 99%

“…139 single nucleotide polymorphisms have been identified in 8 regions of the genome [9]. These polymorphisms (IL2/IL21, IL2RA, CTLA4, IK2F4, HLA, NK-activating ligands, ILBP6, ULBP6, STX17, PRDX5) were found be associated with T cells or the hair follicle.…”

Section: Geneticsmentioning

confidence: 99%

Limited Effectiveness of Platelet-Rich-Plasma Treatment on Chronic Severe Alopecia Areata

Sinclair¹

2014

Hair Therap Transplantat

View full text Add to dashboard Cite

Alopecia Areata (AA) is a common non-scarring alopecia that usually presents as well circumscribed patches of sudden hair loss that affects 0.1-0.2% of the population. The aetiology is thought to be both genetic and autoimmune in nature. 139 single nucleotide polymorphisms have been identified in 8 regions of the genome and are found to be associated with T cells or the hair follicle. Furthermore, patients with AA have been found to have an increased frequency of hair follicle-specific auto-antibodies. The diagnosis of AA is usually made on clinical grounds, and further investigations are not usually indicated. Intralesional corticosteroids remain the treatment of choice. Systemic steroids are also highly effective; however side effects make them less desirable to both patients and physicians. Other treatment options available include anthralin, minoxidil, topical immunotherapy and these treatments will be discussed further in depth in this chapter. The morbidity of AA is largely psychological; therefore the successful treatment of AA should include focusing on the improvement of the psychological impact of this condition.

show abstract

Genome-wide association study in alopecia areata implicates both innate and adaptive immunity

Cited by 678 publications

References 38 publications

Single nucleotide polymorphisms in the promoter regions of Foxp3 and ICOSLG genes are associated with Alopecia Areata

Single nucleotide polymorphisms in the promoter regions of Foxp3 and ICOSLG genes are associated with Alopecia Areata

Meta-analysis reveals an association of PTPN22 C1858T with autoimmune diseases, which depends on the localization of the affected tissue

Limited Effectiveness of Platelet-Rich-Plasma Treatment on Chronic Severe Alopecia Areata

Contact Info

Product

Resources

About