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Abstract Number: 2964

Association Analysis of Apolipoprotein B and Very Low-Density Lipoprotein with Hyperuricemia and Gout

Humaira Rasheed1, Angela Hsu1, Nicola Dalbeth2, Lisa K. Stamp3, Sally McCormick1 and Tony R. Merriman1, 1Department of Biochemistry, University of Otago, Dunedin, New Zealand, 2Department of Medicine, University of Auckland, Auckland, New Zealand, 3University of Otago, Christchurch, New Zealand

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: gout and hyperuricemia

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Session Information

Session Title: Metabolic and Crystal Arthropathies II: Mechanisms of Disease

Session Type: Abstract Submissions (ACR)

Background/Purpose: Gout results from an innate immune response to monosodium urate (MSU) crystals deposited in joints. Increased very low-density lipoprotein (VLDL) has been associated with gout. Apolipoprotein B (apoB), present on VLDL, regulates neutrophil response to MSU crystals. ApoB has been positively associated with gout and the APOB mRNA-editing gene, A1CF, is associated with urate levels. However the relationship of ApoB and VLDL with gout in the presence of hyperuricemia has not previously been tested. Therefore we tested the association of VLDL and apoB with gout in the presence of hyperuricemia (HU).

Methods: New Zealand European (n = 90) and Māori and Pacific Island (Polynesian) (n = 90) male gout case and control sample sets were divided into normouricemia (NU: serum urate <0.41mmol/L), asymptomatic hyperuricemia (HU: serum urate ≥0.41mmol/L) and gout groups. Gout was classified using the 1997 American Rheumatism Association criteria. Size exclusion chromatography and enzyme-linked immunosorbant assay were used to measure VLDL and apoB. Multivariate linear regression was used to assess the risk of gout and HU per unit change in VLDL and apoB.

Results: Increased levels of VLDL triglycerides (Tg) were observed in the gout sample set compared to NU and HU in European (P=1×10-4 and 2×10-3, respectively) and Polynesian subjects (P=0.042 and 0.019, respectively). This increase was driven by overproduction of VLDL particles in the European subjects and by the Tg-enrichment of existing VLDL particles in the Polynesian subjects. Each mmol/L increase in VLDL Tg was significantly associated with gout in the presence of HU in Europeans, with a similar trend in Polynesians (OR=6.82, P=0.017 and 2.85, P=0.066, respectively). Each μmol/L increase in apoB was associated with a decreased risk of HU (OR=0.47; P=0.046) and, conversely, with increased risk of gout in the presence of HU (OR=4.79; P=0.005: Table 1) in combined sample set. 

Conclusion: Increased VLDL Tg is associated with the risk of gout in the presence of HU. If genetic approaches indicate evidence for causality of VLDL in gout, this would provide further justification for clinical trials examining the effects of fibrates as a treatment option in gout.

                          Table 1: Analysis of association of VLDL Tg and apo B associated traits with gout and hyperuricemia

 

 

Association with gout risk

 

Association with Hyperuricemia

 

NU vs. Gout

HU vs. Gout

NU vs. HU and gout

 

OR [95%CI]

P

OR [95%CI]

P

OR [95%CI]

P

VLDL Tg

 

 

 

 

 

 

Europeans

3.51 [0.94-13.18]

0.063

6.82 [1.40-33.12]

0.017

2.51 [0.66-9.55]

0.18

Polynesians

Combined

 

1.05 [0.37-2.97]

1.92 [0.95-3.86]

 

0.92

0.068

2.85 [0.93-8.72]

3.43 [1.56-7.56]

 

0.066

0.002

0.89 [0.39-2.07]

1.28 [0.67-2.43]

 

0.80

0.45

 

Total apo B

 

 

 

 

 

 

Europeans

1.24 [0.32-4.87]

0.76

3.13 [0.92-10.65]

0.067

0.58 [0.20-1.67]

0.32

Polynesians

0.23 [0.04-1.34]

0.10

12.43 [0.68-227.45]

0.089

0.19 [0.05-0.82]

0.026

Combined

0.85 [0.37-1.97]

0.70

4.79 [1.60-14.37]

0.005

0.47 [0.22-0.99]

0.046

 All associations are adjusted for age, BMI, type 2 diabetes, SSB intake (drinks/day), alcohol intake (drinks/week), estimated glomerular filtration rate (eGFR) and prescription of lipid-lowering medication. The Polynesian data are also adjusted by number of self-reported Polynesian grandparents. Combined sample sets are additionally adjusted for ethnic class. VLDL Tg and total FPLC Tg are measured in mmol/L. Apo B is measured in μmol/L.


Disclosure:

H. Rasheed,
None;

A. Hsu,
None;

N. Dalbeth,
None;

L. K. Stamp,
None;

S. McCormick,
None;

T. R. Merriman,
None.

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