한빛사논문
- 조회386
Young-Chang Kwon 1,2, Eunji Ha 3, Hyuk-Hee Kwon 4, Dae Jin Park 4, Jung-Min Shin 4, Young Bin Joo 1,4, Won Tae Chung 5, Dae-Hyun Yoo 1,4, Hye-Soon Lee 1,2,4, Kwangwoo Kim 3*, Sang-Cheol Bae 1,2,4*, So-Young Bang 1,2,4*
1Hanyang University Institute for Rheumatology Research, Seoul, Republic of Korea.
2Hanyang Institute of Bioscience and Biotechnology, Hanyang University, Seoul, Republic of Korea.
3Department of Biology and Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul, Republic of Korea.
4Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea.
5Department of Internal Medicine, College of Medicine, Dong-A University, Pusan, Republic of Korea.
YCK and EH contributed equally.
CORRESPONDING AUTHORS : Kwangwoo Kim PhD, Sang-Cheol Bae MD, PhD, MPH, So-Young Bang MD, PhD
Abstract
Objective: Systemic lupus erythematosus (SLE) is a highly heritable complex disorder with heterogeneous clinical manifestations. We aimed to identify the genetic risk load using clinical and serological manifestations in SLE patients.
Methods: We genotyped a total of 1,655 Korean patients with SLE (n=1,243 as a discovery set and n=412 as a replication set) using a customized genome-wide SNP array, KoreanChip. A weighted genetic risk score (wGRS) for an individual was calculated from 112 well-validated non-HLA SNPs and HLA of SLE-risk loci. Associations of individual wGRS with clinical SLE sub-phenotypes and autoantibodies were analyzed using multivariable linear or logistic regression adjusted by onset-age, sex, disease duration.
Results: Childhood-onset SLE (<16 years) conferred the highest genetic risk, compared with adult-onset (16-50 years) or late-onset (>50 years) SLE (p=6.8×10-6 ). High wGRS significantly increased associations with SLE manifestations, regardless of onset-age, sex, and disease duration. Individual wGRS significantly correlated positively with more clinical ACR criteria (β=0.143, p=1.8×10-6 ). Sub-phenotype analysis revealed significant associations between the highest and lowest wGRS-quartile with the risk of renal disorder (HR=1.74, p=2.2×10-8 ) and anti-Sm-antibody production (HR=1.85, p=2.8×10-5 ). Higher wGRS markedly modulated the pathogenesis of proliferative and membranous lupus nephritis [class III or IV (HR=1.98, p=1.6×10-5 ); class V (HR=2.79, p=1.0×10-3 )], especially lupus nephritis class V in anti-Sm-positive SLE (AUC=0.68, p=1.8×10-4 ).
Conclusion: The SLE patients with higher wGRS tended to have earlier onset-age, anti-Sm antibody, and more diverse clinical phenotypes. Genetic profiling may predict high risk for lupus nephritis and diverse clinical course in SLE patients.
논문정보
- Research article
- 2023년 04월 (BRIC 등록일 2023-05-15)
- 국내 연구진
- 의약학 > 응용의학
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