Acta Dermato-Venereologica 99-1CompleteContent | Page 21

84 INVESTIGATIVE REPORT Identification of a Single Nucleotide Polymorphism in NFKBIA with Different Effects on Psoriatic Arthritis and Cutaneous Psoriasis in China Qing ZHAO 1–3 , Yonghu SUN 1–3 , Xi’an FU 1–3 , Zhenzhen WANG 2,3 , Gongqi YU 2,3 , Zhenhua YUE 1–3 , Yaru WANG 2–4 , Huimin ZHANG 2–4 , Chuan WANG 2,3 , Hong LIU 1,2,5 , Qing YANG 2,3 and Furen ZHANG 1–5 Department of Dermatology, Shandong Provincial Hospital for Skin Disease, Shandong University, 2 Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Sciences, Jinan, Shandong, 3 Shandong Provincial Key Laboratory for Dermatovenereology, 4 School of Medicine and Life Science, University of Jinan-Shandong Academy of Medical Sciences, Jinan, Shandong, and 5 Binzhou Medical University, Yantai, Shandong, China 1 Genome-wide association studies have recently identi- fied a number of non-major histocompatibility complex regions associated with psoriatic arthritis. However, data on Chinese patients with psoriatic arthritis and the differences between psoriatic arthritis and cuta- neous psoriasis are limited. This study genotyped 12 single nucleotide polymorphisms in 379 patients with psoriatic arthritis, 376 with cutaneous psoriasis, and 760 healthy controls using Sequenom’s Mass ARRAY system. The aim of the study was to expand the da- tabase for psoriatic arthritis and cutaneous psoriasis, and develop a genetic prediction system for the early diagnosis of psoriatic arthritis in the Chinese popula- tion. One variant in NFKBIA, rs12883343, had a sig- nificantly different association with psoriatic arthritis than with cutaneous psoriasis (p  = 4.93×10 –10 , odds ra- tio 2.371). This suggests that there are differences in the pathogenesis of psoriatic arthritis and cutaneous psoriasis. Key words: psoriatic arthritis; cutaneous psoriasis; NFKBIA. Accepted Aug 31, 2018; Epub ahead of print Sep 3, 2018 Acta Derm Venereol 2019; 99: 84–88. Corr: Furen Zhang and Qing Yang, Department of Dermatology and Ve- nereology, Shandong Provincial Institute of Dermatology and Venereo- logy, Shandong Academy of Medical Science, 27397 Jingshi Lu, Shan- dong Province, Jinan 250022, China. E-mails: [email protected]; [email protected] P soriatic arthritis (PsA) is an inflammatory arthritis as- sociated with psoriasis, characterized by seronegative rheumatoid factor. Among patients with psoriasis, the prevalence of PsA varies from 6% in the USA to 42% in South Africa (1), while published figures indicate lower prevalence rates in Asian countries (2), such as Korea (9%) (3) and Japan (1%) (4). In China, the prevalence of PsA has been estimated as 5.8% (5) based on a large cross-sectional observational study. Although the exact mechanism of PsA is unclear, host genetics, immuno- logical, and environmental factors are thought to play a role (6). With the development of genome-wide association studies (GWAS), 4 PsA GWAS have been published to date. Together with candidate loci analyses and Immu- doi: 10.2340/00015555-3027 Acta Derm Venereol 2019; 99: 84–88 SIGNIFICANCE A number of novel psoriatic arthritis genetic susceptibility loci have been identified recently, but data on their associa- tion with Chinese psoriatic arthritis patients are limited. In addition, the data of differences between psoriatic arthritis and cutaneous psoriasis are lacking. We performed a ge- netic study in a Chinese population to expand the data- base for psoriatic arthritis and cutaneous psoriasis and to develop a genetic prediction model for early diagnosis of psoriatic arthritis. nochip array studies, 15 non-major histocompatibility complex (non-MHC) regions associated with PsA have shown statistical significance (p ≤ 5×10 –8 ). These include IL-12B (7–10), IL-23R (7, 10), TNIP1 (7, 8, 10), TRA- F3IP2 (7, 9, 11, 12), CSF2 (7), FBXL19 (13), REL (7, 14), RUNX3 (15), TYK2 (7, 10), NOS2 (16), PTPN22 (16), IFNLR1 (7), IFIH1 (7), NFKBIA (7) and STAT2 (10). Current genetic studies have suggested that key pathways in the pathogenesis of PsA include the NFκB and IFN signalling pathway, and adaptive immune re- sponses involving CD8 + T cells and CD4 + T helper (Th) 17-cell signalling (17–20). Clinically, psoriasis vulgaris (PsV) is characterized by sharply demarcated, scaly, erythematous plaques. As with PsV, PsA has the common manifestation of skin lesions, but additionally manifests with peripheral arthritis, enthesitis, dactylitis, uveitis, and spondylitis (20). GWAS and candidate loci analyses have revealed differences in their genetic architecture (7). Significant differences in the strength of association between pso- riasis and the MHC have been observed. It has been reported that the human leukocyte-associated antigen (HLA)-Cw*0602 is strongly associated with PsV (21), while HLA-B*27 plays an important role in PsA (22). Winchester et al. (22) hypothesized that the MHC mole- cules encoded by HLA-C*0602 presented skin-specific self-peptides to T cells, whereas B*27 molecules are mediators for the primary response to a cutaneous and joint antigen. Currently, there are 13 non-MHC regions with a nominally significant (p < 0.05) difference in their association for these 2 forms of psoriasis (7). However, This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2019 Acta Dermato-Venereologica.