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LP-099 High genetic risk loads increase the risk of lupus nephritis in Koreans
  1. Young-Chang Kwon1,
  2. Eunji Ha2,
  3. Hyuk-Hee Kwon3,
  4. Dae Jin Park3,
  5. Jung-Min Shin3,
  6. Young Bin Joo3,
  7. Won Tae Chung4,
  8. Dae-Hyun Yoo1,3,
  9. Hye-Soon Lee1,3,
  10. Kwangwoo Kim2,
  11. Sang-Cheol Bae1,3 and
  12. So-Young Bang1,3
  1. 1Hanyang University Institute for Rheumatology Research, Hanyang University, Republic of Korea
  2. 2Department of Biology and Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Republic of Korea
  3. 3Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Republic of Korea
  4. 4Department of Rheumatology, Dong-A University, Republic of Korea


Background Systemic lupus erythematosus (SLE) is an autoimmune disease with heterogeneous manifestations and unpredictable outcome. We aimed to identify the genetic contributions on clinical and serological manifestations in Korean patients with SLE.

Methods The patients with SLE were enrolled including a discovery cohort and a replication cohort from the Korean population (n = 1,655). Weighted genetic risk score (wGRS) were calculated by SLE risk loci [112 well-validated non-HLA SNPs and HLA-DRB1 haplotype] based on genome-wide association study. Individual wGRS was tested for associations with clinical sub-phenotypes of SLE by using multivariable linear regression or logistic regression.

Results Increasing wGRS was significantly associated with more diverse manifestation of SLE, regardless of onset age, sex and disease duration. The SLE patients with high wGRS-quartile were significantly associated 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) compared to patients with low wGRS-quartile.

We found that wGRS influenced on the development of proliferative lupus nephritis (LN) [class III or IV (HR=1.98, p=1.6×10−5)] and membranous LN [class V (HR=2.79, p=1.0×10−3)]. Moreover, increasing wGRS had the strongest effect on the development of LN class V in anti-Sm positive SLE (AUC=0.681, p= 1.8×10−4).

Conclusions The higher wGRS, which implicated in pathogenesis of SLE, increased the risk to develop lupus nephritis and anti-Sm antibody production. Our study provided that genetic risk loads could predict the clinical outcome in SLE.

  • genetic risk score
  • lupus nephritis
  • systemic lupus erythematosus

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