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Sci Rep. 2018 Jul 2;8(1):9962. doi: 10.1038/s41598-018-28128-z.

Genetic variants in systemic lupus erythematosus susceptibility loci, XKR6 and GLT1D1 are associated with childhood-onset SLE in a Korean cohort.

Author information

1
Department of Rheumatology, St. Vincent's Hospital, The Catholic University of Korea, Suwon, Republic of Korea.
2
Department of Biology, Kyung Hee University, Seoul, Republic of Korea.
3
Division of Rheumatology and Immunology, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA.
4
Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
5
Department of Biology, Kyung Hee University, Seoul, Republic of Korea. kkim@khu.ac.kr.
6
Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea. scbae@hanyang.ac.kr.

Abstract

Impact of genetic variants on the age of systemic lupus erythematosus (SLE) onset was not fully understood. We investigated a cumulative effect of SLE-risk variants on the age of SLE onset and scanned genome-wide SNPs to search for new risk loci of childhood-onset SLE (cSLE). We analyzed 781 Korean single-center SLE subjects who previously genotyped by both Immunochip and genome-wide SNP arrays. Individual genetic risk scores (GRS) from well-validated SLE susceptibility loci were calculated and tested for their association with cSLE (<16 years at onset). Single-variant association tests were performed using a multivariable logistic regression adjusting for population stratification. GRS from SLE susceptibility loci was significantly higher in cSLE than aSLE (p = 1.23 × 10-3). Two SNPs, rs7460469 in XKR6 (p = 1.26 × 10-8, OR = 5.58) and rs7300146 in GLT1D1 p = 1.49 × 10-8, OR = 2.85), showed the most significant associations with cSLE. The model consisting of GRS of SLE and two newly identified loci showed an area under curve (AUC) of 0.71 in a receiver operating characteristics (ROC) curve for prediction of cSLE. In conclusion, cSLE is associated with a high cumulative SLE-risk effect and two novel SNPs rs7460469 and rs7300146, providing the first predictive model for cSLE in Koreans.

PMID:
29967481
PMCID:
PMC6028392
DOI:
10.1038/s41598-018-28128-z
[Indexed for MEDLINE]
Free PMC Article

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