Open AccessBrief Report: Single‐nucleotide polymorphisms in VKORC1 are risk factors for systemic lupus erythematosus in Asians
Author(s) -
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.,
RamseyGoldman Rosalind,
Reveille John D.,
Vila Luis M.,
Petri Michelle,
Kimberly Robert P.,
Feng Xuebing,
Sun Lingyun,
Shen Nan,
Li Wei,
Lu JianXin,
Wakeland Edward K.,
Li QuanZhen,
Yang Wanling,
Lau YuLung,
Liu FeiLan,
Chang DehMing,
Yu ChackYung,
Song Yeong W.,
Tsao Betty P.,
Criswell Lindsey A.
Publication year - 2013
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.37751
Subject(s) - cohort , medicine , single nucleotide polymorphism , odds ratio , case control study , immunology , genetics , genotype , biology , gene
Objective The 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. Methods Patients 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. Results Two 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. Conclusion Genetic 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.