Rheumatoid Arthritis

Association of Paraoxonase 1 Gene Polymorphism and Enzyme Activity With Carotid Plaque in Rheumatoid Arthritis

Corresponding Author

Christina Charles-Schoeman

David Geffen School of Medicine, University of California, Los Angeles

Dr. Charles-Schoeman has received consulting fees and speaking fees from Pfizer (more than $10,000) and has received research grants from Bristol-Myers Squibb and Pfizer.

David Geffen School of Medicine, University of California, Los Angeles, 1000 Veteran Avenue, Room 32-59, Los Angeles, CA 90095-1670. E-mail: [email protected]Search for more papers by this author

Yuen Yin Lee,

Yuen Yin Lee

David Geffen School of Medicine, University of California, Los Angeles

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Ani Shahbazian,

Ani Shahbazian

David Geffen School of Medicine, University of California, Los Angeles

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Alan H. Gorn,

Alan H. Gorn

David Geffen School of Medicine, University of California, Los Angeles

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John FitzGerald,

John FitzGerald

David Geffen School of Medicine, University of California, Los Angeles

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Veena K. Ranganath,

Veena K. Ranganath

David Geffen School of Medicine, University of California, Los Angeles

Dr. Ranganath has received consulting fees from UCB (less than $10,000) and has received research grants from UCB and Bristol-Myers Squibb.

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Mihaela Taylor,

Mihaela Taylor

David Geffen School of Medicine, University of California, Los Angeles

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Nagesh Ragavendra,

Nagesh Ragavendra

David Geffen School of Medicine, University of California, Los Angeles

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Maureen McMahon,

Maureen McMahon

David Geffen School of Medicine, University of California, Los Angeles

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David Elashoff,

David Elashoff

David Geffen School of Medicine, University of California, Los Angeles

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Srinivasa T. Reddy,

Srinivasa T. Reddy

David Geffen School of Medicine, University of California, Los Angeles

Search for more papers by this author

Christina Charles-Schoeman,

Corresponding Author

Christina Charles-Schoeman

David Geffen School of Medicine, University of California, Los Angeles

Dr. Charles-Schoeman has received consulting fees and speaking fees from Pfizer (more than $10,000) and has received research grants from Bristol-Myers Squibb and Pfizer.

David Geffen School of Medicine, University of California, Los Angeles, 1000 Veteran Avenue, Room 32-59, Los Angeles, CA 90095-1670. E-mail: [email protected]Search for more papers by this author

Yuen Yin Lee,

Yuen Yin Lee

David Geffen School of Medicine, University of California, Los Angeles

Search for more papers by this author

Ani Shahbazian,

Ani Shahbazian

David Geffen School of Medicine, University of California, Los Angeles

Search for more papers by this author

Alan H. Gorn,

Alan H. Gorn

David Geffen School of Medicine, University of California, Los Angeles

Search for more papers by this author

John FitzGerald,

John FitzGerald

David Geffen School of Medicine, University of California, Los Angeles

Search for more papers by this author

Veena K. Ranganath,

Veena K. Ranganath

David Geffen School of Medicine, University of California, Los Angeles

Dr. Ranganath has received consulting fees from UCB (less than $10,000) and has received research grants from UCB and Bristol-Myers Squibb.

Search for more papers by this author

Mihaela Taylor,

Mihaela Taylor

David Geffen School of Medicine, University of California, Los Angeles

Search for more papers by this author

Nagesh Ragavendra,

Nagesh Ragavendra

David Geffen School of Medicine, University of California, Los Angeles

Search for more papers by this author

Maureen McMahon,

Maureen McMahon

David Geffen School of Medicine, University of California, Los Angeles

Search for more papers by this author

David Elashoff,

David Elashoff

David Geffen School of Medicine, University of California, Los Angeles

Search for more papers by this author

Srinivasa T. Reddy,

Srinivasa T. Reddy

David Geffen School of Medicine, University of California, Los Angeles

Search for more papers by this author

First published: 05 August 2013

https://doi.org/10.1002/art.38118

Citations: 44

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Abstract

Objective

To investigate the relationship of genetic and biochemical determinants of paraoxonase 1 activity to carotid plaque as a surrogate marker of cardiovascular (CV) risk in patients with rheumatoid arthritis (RA).

Methods

The relationships between paraoxonase 1 activity, PON1 genotype (for the functional polymorphism at position 192), and carotid plaque presence were determined in 168 RA patients. After an overnight fast, blood was collected for lipoprotein analysis, and paraoxonase 1 activity was measured using paraoxon as the substrate. The PON1 Q192R genotype was determined for all patients. Lipoprotein cholesterol levels, traditional CV risk factors, medication use, and RA disease characteristics were assessed for all patients.

Results

Paraoxonase 1 activity values in the RA patients were highest for the RR genotype, intermediate for the QR genotype, and lowest for the QQ genotype (P < 0.0001). Compared to patients with either the QQ genotype or the QR genotype, patients with the RR genotype demonstrated decreased risk of carotid plaque on multivariate analysis, controlling for traditional CV risk factors, high-sensitivity C-reactive protein levels, prednisone use, and cholesterol-lowering medication use (P < 0.05). Additional multivariate logistic regression analysis controlling for the above factors also revealed a significant association of plasma paraoxonase 1 activity with carotid plaque in RA patients. Lower plasma paraoxonase 1 activity was associated with increased risk of carotid plaque (P < 0.05).

Conclusion

The current findings suggest a relationship of the genetic determinants and activity of paraoxonase 1 to CV risk in RA patients, as assessed by the presence or absence of carotid plaque. Further CV outcome studies are warranted to validate the utility of paraoxonase 1 as a biomarker of CV risk in patients with RA.

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Volume65, Issue11

November 2013

Pages 2765-2772

Association of Paraoxonase 1 Gene Polymorphism and Enzyme Activity With Carotid Plaque in Rheumatoid Arthritis

Abstract

Objective

Methods

Results

Conclusion

REFERENCES

Citing Literature

References

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Association of Paraoxonase 1 Gene Polymorphism and Enzyme Activity With Carotid Plaque in Rheumatoid Arthritis

Abstract

Objective

Methods

Results

Conclusion

REFERENCES

Citing Literature

References

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