Brief Report: Single‐nucleotide polymorphisms in VKORC1 are risk factors for systemic lupus erythematosus in Asians1. Issue 1 (27th December 2012)

• Record Type: Journal Article
• Authors: 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.; Hwee Siew Howe and the Tan Tock Seng Hospital Systemic Lupus Erythematosus Study Group; Tsao, Betty P.; Criswell, Lindsey A.;
• Is Part Of: Arthritis and rheumatism. Volume 65:Issue 1(2013:Jan.)
• Page Start: 211
• Page End: 215
• Publication Date: 2012-12-27
• Subjects: Arthritis -- Periodicals; Rheumatism -- Periodicals; Arthritis -- Periodicals; Rheumatic Diseases -- Periodicals; Rhumatisme -- Périodiques; Arthrite -- Périodiques; 616.72
• DOI: 10.1002/art.37751
• Languages: English
• ISSNs: 0004-3591

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="abs1-1" sec-type="section"> <title>Objective</title> <p>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.</p> </sec> <sec id="abs1-2" sec-type="section"> <title>Methods</title> <p>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.</p> </sec> <sec id="abs1-3" sec-type="section"> <title>Results</title> <p>Two genetic variants in the gene <italic>VKORC1</italic> were highly significant in both the discovery and replication cohorts: rs9934438 (in the discovery cohort, odds ratio [OR] 2.45, <italic>P</italic> = 2 × 10<sup>−9</sup>; in the replication cohort, OR 1.54, <italic>P</italic> = 4 × 10<sup>−6</sup>) and rs9923231 (in the discovery cohort, OR 2.40, <italic>P</italic> = 6 × 10<sup>−9</sup>; in the replication cohort, OR 1.53, <italic>P</italic> = 5 × 10<sup>−6</sup>). These associations were significant in the replication cohort after adjustment for intra‐Asian ancestry: for rs9934438, OR 1.34, <italic>P</italic> = 0.0029; for rs9923231, OR 1.34, <italic>P</italic> = 0.0032.</p> </sec> <sec id="abs1-4" sec-type="section"> <title>Conclusion</title> <p>Genetic variants in <italic>VKORC1</italic>, 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.</p> </sec> </abstract>