title: Brief Report: Single-nucleotide polymorphisms in VKORC1 are risk factors for systemic lupus erythematosus in Asians.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of California, San Francisco, CA 94143, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Kaiser
authors.forename: Kimberly E
authors.initials: KE
authors.lastname: Taylor
authors.forename: Yun
authors.initials: Y
authors.lastname: Deng
authors.forename: Jian
authors.initials: J
authors.lastname: Zhao
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Li
authors.forename: Joanne
authors.initials: J
authors.lastname: Nititham
authors.forename: Monica
authors.initials: M
authors.lastname: Chang
authors.forename: Joseph
authors.initials: J
authors.lastname: Catanese
authors.forename: Ann B
authors.initials: AB
authors.lastname: Begovich
authors.forename: Elizabeth E
authors.initials: EE
authors.lastname: Brown
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Edberg
authors.forename: Gerald
authors.initials: G
authors.lastname: McGwin
authors.forename: Graciela S
authors.initials: GS
authors.lastname: Alarcón
authors.forename: Rosalind
authors.initials: R
authors.lastname: Ramsey-Goldman
authors.forename: John D
authors.initials: JD
authors.lastname: Reveille
authors.forename: Luis M
authors.initials: LM
authors.lastname: Vila
authors.forename: Michelle
authors.initials: M
authors.lastname: Petri
authors.forename: Robert P
authors.initials: RP
authors.lastname: Kimberly
authors.forename: Xuebing
authors.initials: X
authors.lastname: Feng
authors.forename: Lingyun
authors.initials: L
authors.lastname: Sun
authors.forename: Nan
authors.initials: N
authors.lastname: Shen
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Jian-Xin
authors.initials: JX
authors.lastname: Lu
authors.forename: Edward K
authors.initials: EK
authors.lastname: Wakeland
authors.forename: Quan-Zhen
authors.initials: QZ
authors.lastname: Li
authors.forename: Wanling
authors.initials: W
authors.lastname: Yang
authors.forename: Yu-Lung
authors.initials: YL
authors.lastname: Lau
authors.forename: Fei-Lan
authors.initials: FL
authors.lastname: Liu
authors.forename: Deh-Ming
authors.initials: DM
authors.lastname: Chang
authors.forename: Chack-Yung
authors.initials: CY
authors.lastname: Yu
authors.forename: Yeong W
authors.initials: YW
authors.lastname: Song
authors.forename: Betty P
authors.initials: BP
authors.lastname: Tsao
authors.forename: Lindsey A
authors.initials: LA
authors.lastname: Criswell
mesh_terms: D000328:Adult; D044466:Asian People; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006487:Hemostasis / Q000235:genetics*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D020246:Venous Thrombosis / Q000235:genetics*; D064417:Vitamin K Epoxide Reductases
chemical_list: D006899:Mixed Function Oxygenases; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases