PTPN22 profile indicates a novel risk group in Alopecia areata

Abstract Alopecia areata (AA) is a genetically determined autoimmune hair loss disorder. A polymorphism in protein tyrosine phosphatase N22 ( PTPN22 ), which normally suppresses T-cell proliferation, has been associated with human autoimmune disease, including AA in European populations. PTPN22 genotype frequency in known to vary geographically. Accordingly, we conducted a case-control study of the PTPN22 1858C/1858T (C1858T) genotype frequency in North American Caucasians and non-Caucasians. Allele status was determined in 365 AA patients, 196 healthy related control subjects (RC) and 77 unrelated healthy control subjects (UrC). We found that AA patients are more likely to carry the PTPN22 C1858T genotype than UrCs ( p  = 0.075), and this association reached significance in patients with the most severe disease presentation (Alopecia universalis vs. UrC, p  = 0.024). PTPN22 C1858T genotype frequency in RC did not differ from AA patients ( p  = 0.657), but was significantly increased in comparison with UrC ( p  = 0.050). PTPN22 1858C/T genotype frequency increased in related control subjects most closely associated with patients (one family members of AA patients vs. UrC subjects, p  = 0.040). Our data suggests that AA patients (particularly those that are severely affected) and closely related control subjects may belong to a shared inheritance group with increased disease risk, distinct from secondary and tertiary relatives and unrelated individuals. These findings have implications for the study of candidate genes and susceptibility to AA that may influence future clinical monitoring of unaffected, but closely related family members of patients.