Brief Report: Single‐nucleotide polymorphisms in VKORC1 are risk factors for systemic lupus erythematosus in Asians
Year: 2012
Type: article
Study design: Observational Study
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. 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.
Source: Arthritis & Rheumatism
DOI: 10.1002/art.37751
Authors: Rachel Kaiser, Kimberly E. Taylor, Yun Deng, Jian Zhao, Yonghong Li, Joanne Nititham, Monica Chang, Joseph Catanese, Ann B. Begovich, Elizabeth E. Brown, Jeffrey C. Edberg, Gerald McGwin, Graciela S. Alarcón, Rosalind Ramsey‐Goldman, John D. Reveille, Luis M. Vila, Michelle Petri, Robert P. Kimberly, Xuebing Feng, Lingyun Sun, Nan Shen, Wei Li, Jian‐Xin Lu, Edward K. Wakeland, Quan‐Zhen Li, Wanling Yang, Yu‐Lung Lau, Fei‐Lan Liu, Deh‐Ming Chang, Chack‐Yung Yu, Yeong W. Song, Betty P. Tsao, Lindsey A. Criswell
Institutions: University of California, San Francisco, Russell/Engleman Rheumatology Research Center, University of California, Los Angeles, F. Hoffmann-La Roche AG, University of Alabama at Birmingham, UAB Medicine, Northwestern University, The University of Texas Health Science Center at Houston, University of Puerto Rico, Medical Sciences Campus, University of Puerto Rico System, Johns Hopkins University, Johns Hopkins Medicine, Nanjing Drum Tower Hospital, Nanjing University, Shanghai Jiao Tong University, Renji Hospital, Ministry of Education of the People's Republic of China, Wenzhou Medical University, The University of Texas Southwestern Medical Center, University of Hong Kong, Taipei Medical University, National Defense Medical Center, Nationwide Children's Hospital, Abigail Wexner Research Institute, The Ohio State University, Seoul National University, Tan Tock Seng Hospital, National Healthcare Group
Language: English
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: NIAMS Multidisciplinary Clinical Research Center, TESTING SLE CANDIDATE LOCI USING CASES AND THEIR PARENTS, UAB Center for Clinical and Translational Science (CCTS) UL1, General Clinical Research Center, NIAMS Multidisciplinary Clinical Research Center, MULTIPURPOSE ARTHRITIS AND MUSCULOSKELETAL DISEASES CENT, G3593991805, Hopkins Lupus Cohort, G480404446, The Genetic Epidemiology of RA and SLE, Program Project in the Genetics of SLE, Multidisciplinary Clinical and Translational Science (MCTS) Program (UL1), Patient Oriented Research: Systemic Lupus Erythematosus, Multidisciplinary Clinical Research Center in Rheumatology, Association of Positional Candidate Gene Variants with SLE
OpenAlex ID: W1982950986