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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,
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Journal Compilation © 2019 Acta Dermato-Venereologica.