Single-nucleotide polymorphisms in VKORC1 are risk factors for systemic lupus erythematosus in Asians

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

doi:10.1002/art.37751

Single-nucleotide polymorphisms in VKORC1 are risk factors for systemic lupus erythematosus in Asians

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 SunNan 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

School of Medicine

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

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.

Original language	English (US)
Pages (from-to)	211-215
Number of pages	5
Journal	Arthritis and rheumatism
Volume	65
Issue number	1
DOIs	https://doi.org/10.1002/art.37751
State	Published - Jan 2013

ASJC Scopus subject areas

Immunology and Allergy
Rheumatology
Immunology
Pharmacology (medical)

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Kaiser, R., Taylor, K. E., Deng, Y., Zhao, J., Li, Y., Nititham, J., Chang, M., Catanese, J., Begovich, A. B., Brown, E. E., Edberg, J. C., McGwin, G., Alarcón, G. S., Ramsey-Goldman, R., Reveille, J. D., Vila, L. M., Petri, M., Kimberly, R. P., Feng, X., ... Criswell, L. A. (2013). Single-nucleotide polymorphisms in VKORC1 are risk factors for systemic lupus erythematosus in Asians. Arthritis and rheumatism, 65(1), 211-215. https://doi.org/10.1002/art.37751

Kaiser, R, Taylor, KE, Deng, Y, Zhao, J, Li, Y, Nititham, J, Chang, M, Catanese, J, Begovich, AB, Brown, EE, Edberg, JC, McGwin, G, Alarcón, GS, Ramsey-Goldman, R, Reveille, JD, Vila, LM, Petri, M, Kimberly, RP, Feng, X, Sun, L, Shen, N, Li, W, Lu, JX, Wakeland, EK, Li, QZ, Yang, W, Lau, YL, Liu, FL, Chang, DM, Yu, CY, Song, YW, Tsao, BP & Criswell, LA 2013, 'Single-nucleotide polymorphisms in VKORC1 are risk factors for systemic lupus erythematosus in Asians', Arthritis and rheumatism, vol. 65, no. 1, pp. 211-215. https://doi.org/10.1002/art.37751

@article{7c743b243a5740299bd9dbe66f30f8b6,

title = "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. 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.",

author = "Rachel Kaiser and Taylor, {Kimberly E.} and Yun Deng and Jian Zhao and Yonghong Li and Joanne Nititham and Monica Chang and Joseph Catanese and Begovich, {Ann B.} and Brown, {Elizabeth E.} and Edberg, {Jeffrey C.} and Gerald McGwin and Alarc{\'o}n, {Graciela S.} and Rosalind Ramsey-Goldman and Reveille, {John D.} and Vila, {Luis M.} and Michelle Petri and Kimberly, {Robert P.} and Xuebing Feng and Lingyun Sun and Nan Shen and Wei Li and Lu, {Jian Xin} and Wakeland, {Edward K.} and Li, {Quan Zhen} and Wanling Yang and Lau, {Yu Lung} and Liu, {Fei Lan} and Chang, {Deh Ming} and Yu, {Chack Yung} and Song, {Yeong W.} and Tsao, {Betty P.} and Criswell, {Lindsey A.}",

year = "2013",

month = jan,

doi = "10.1002/art.37751",

language = "English (US)",

volume = "65",

pages = "211--215",

journal = "Arthritis and rheumatism",

issn = "0004-3591",

publisher = "John Wiley and Sons Ltd",

number = "1",

}

TY - JOUR

T1 - Single-nucleotide polymorphisms in VKORC1 are risk factors for systemic lupus erythematosus in Asians

AU - Kaiser, Rachel

AU - Taylor, Kimberly E.

AU - Deng, Yun

AU - Zhao, Jian

AU - Li, Yonghong

AU - Nititham, Joanne

AU - Chang, Monica

AU - Catanese, Joseph

AU - Begovich, Ann B.

AU - Brown, Elizabeth E.

AU - Edberg, Jeffrey C.

AU - McGwin, Gerald

AU - Alarcón, Graciela S.

AU - Ramsey-Goldman, Rosalind

AU - Reveille, John D.

AU - Vila, Luis M.

AU - Petri, Michelle

AU - Kimberly, Robert P.

AU - Feng, Xuebing

AU - Sun, Lingyun

AU - Shen, Nan

AU - Li, Wei

AU - Lu, Jian Xin

AU - Wakeland, Edward K.

AU - Li, Quan Zhen

AU - Yang, Wanling

AU - Lau, Yu Lung

AU - Liu, Fei Lan

AU - Chang, Deh Ming

AU - Yu, Chack Yung

AU - Song, Yeong W.

AU - Tsao, Betty P.

AU - Criswell, Lindsey A.

PY - 2013/1

Y1 - 2013/1

N2 - 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.

AB - 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.

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Single-nucleotide polymorphisms in VKORC1 are risk factors for systemic lupus erythematosus in Asians

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