PMC:4129407 / 26235-27806 JSONTXT

{"project":"2_test","denotations":[{"id":"25087609-1371304-2044438","span":{"begin":447,"end":449},"obj":"1371304"},{"id":"25087609-19232079-2044439","span":{"begin":897,"end":898},"obj":"19232079"},{"id":"25087609-24656864-2044440","span":{"begin":1071,"end":1073},"obj":"24656864"}],"text":"HLA-B amino acid position 45 is the driving MHC position that modulates differential risk of PsA and PsV. The effect of Glu at HLA-B position 45 confers substantial risk of psoriatic arthritis and explains previously reported associations at HLA-B∗27. This site is located within the binding groove of HLA-B and is classified as one of the functional pockets influencing receptor cell-surface expression or antigen peptide binding or presentation.40 Being able to clinically distinguish those individuals who have isolated skin disease (PsC) from those who develop joint disease (PsA) has clinical importance. PsA often occurs in addition to psoriatic skin disease and almost always requires systemic therapy, for example, with anti-TNF or other biologic medications, for the prevention of destructive joint disease. In contrast, PsC can in many instances be managed with topical treatments alone.3 Our findings might contribute to utilizing information on HLA variants to improve diagnostic approaches for clinical subphenotypes, as suggested for other complex diseases.26 There is a possibility that the HLA-B45 amino acid residue tags other HLA-B driving risk variants at other amino acid sites, although we observed only limited LD between these sites (Figure S4). We also note that our method of evaluating OR heterogeneity (i.e., pheterogeneity) might be conservative because of shared control subjects in the PsA and PsC case-control analyses. Further studies will be required for elucidating the functional mechanisms that result in differential PsA and PsC risk."}