1. Brief Report: Single‐nucleotide polymorphisms in VKORC1 are risk factors for systemic lupus erythematosus in Asians
- Author
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Kaiser, Rachel, Taylor, Kimberly E, Deng, Yun, Zhao, Jian, Li, Yonghong, Nititham, Joanne, Chang, Monica, Catanese, Joseph, Begovich, Ann B, Brown, Elizabeth E, Edberg, Jeffrey C, McGwin, Gerald, Alarcón, Graciela S, Ramsey‐Goldman, Rosalind, Reveille, John D, Vila, Luis M, Petri, Michelle, Kimberly, Robert P, Feng, Xuebing, Sun, Lingyun, Shen, Nan, Li, Wei, Lu, Jian‐Xin, Wakeland, Edward K, Li, Quan‐Zhen, Yang, Wanling, Lau, Yu‐Lung, Liu, Fei‐Lan, Chang, Deh‐Ming, Yu, Chack‐Yung, Song, Yeong W, Group, Hwee Siew Howe and the Tan Tock Seng Hospital Systemic Lupus Erythematosus Study, Tsao, Betty P, and Criswell, Lindsey A
- Subjects
Biological Sciences ,Biomedical and Clinical Sciences ,Health Sciences ,Genetics ,Autoimmune Disease ,Lupus ,Clinical Research ,2.1 Biological and endogenous factors ,Aetiology ,Adult ,Asian People ,Case-Control Studies ,Female ,Genetic Predisposition to Disease ,Genotype ,Hemostasis ,Humans ,Lupus Erythematosus ,Systemic ,Male ,Middle Aged ,Mixed Function Oxygenases ,Polymorphism ,Single Nucleotide ,Risk Factors ,Venous Thrombosis ,Vitamin K Epoxide Reductases ,Hwee Siew Howe and the Tan Tock Seng Hospital Systemic Lupus Erythematosus Study Group ,Clinical Sciences ,Immunology ,Public Health and Health Services ,Arthritis & Rheumatology ,Clinical sciences - Abstract
ObjectiveThe increased risk of thrombosis in systemic lupus erythematosus (SLE) may be partially explained by interrelated genetic pathways for thrombosis and SLE. The present study was undertaken to investigate whether 33 established and novel single-nucleotide polymorphisms (SNPs) in 20 genes involved in hemostasis pathways that have been associated with deep venous thrombosis (DVT) in the general population are risk factors for SLE among Asian subjects.MethodsPatients in the discovery cohort were enrolled in 1 of 2 North American SLE cohorts. Patients in the replication cohort were enrolled in 1 of 4 Asian or 2 North American cohorts. We first genotyped 263 Asian patients with SLE and 357 healthy Asian control subjects for 33 SNPs in the discovery phase, and then genotyped 5 SNPs in up to an additional 1,496 patients and 993 controls in the replication phase. Patients were compared to controls for bivariate association with minor alleles. Principal components analysis was used to control for intra-Asian ancestry in the replication cohort.ResultsTwo genetic variants in the gene VKORC1 were highly significant in both the discovery and replication cohorts: rs9934438 (in the discovery cohort, odds ratio [OR] 2.45, P=2×10(-9); in the replication cohort, OR 1.54, P=4×10(-6)) and rs9923231 (in the discovery cohort, OR 2.40, P=6×10(-9); in the replication cohort, OR 1.53, P=5×10(-6)). These associations were significant in the replication cohort after adjustment for intra-Asian ancestry: for rs9934438, OR 1.34, P=0.0029; for rs9923231, OR 1.34, P=0.0032.ConclusionGenetic variants in VKORC1, which are involved in vitamin K reduction and associated with DVT, correlate with SLE development in Asian subjects. These results suggest that there may be intersecting genetic pathways for the development of SLE and thrombosis.
- Published
- 2013