ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 2148

Association of the Paraoxonase 1 Q192R Genetic Polymorphism with Disease Activity in Dermatomyositis

Sangmee Bae1, Buzand Oganesian2, Tyler Dowd3, Ilana Golub1, Ani Shahbazian4, Jennifer Wang3, Srinivasa T. Reddy5 and Christina Charles-Schoeman1, 1University of California, Los Angeles, Los Angeles, CA, 2Medicine-Rheumatology, University of California, Los Angeles, Los ANgeles, CA, 3UCLA, Los Angeles, CA, 4Medicine-Rheumatology, UCLA David Geffen School of Medicine, Los Angeles, CA, 5Medicine-Cardiology, University of California, Los Angeles, Los Angeles, CA

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords:

Session Information

Date: Tuesday, November 7, 2017

Title: Muscle Biology, Myositis and Myopathies Poster

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose:

Injury to the vascular endothelium is implicated in the pathogenesis of dermatomyositis (DM). Normal high density lipoprotein (HDL) protects the vascular endothelium from damage due to oxidized phospholipids, which accumulate under conditions of oxidative stress and are metabolized by the HDL-associated enzyme, paraoxonase 1 (PON1). The current work evaluates the relationship of the PON1Q192R genetic polymorphism and PON1 activity to disease activity and damage in DM pts.

Methods:

In a cross-sectional cohort of 118 DM pts, the relationships between PON1 activity, PON1 genotype (for the functional polymorphism at position 192), and myositis disease activity and damage were assessed using physician global 5 point Likert and 100 mm visual analogue scales (VAS), CPK levels, and pulmonary function tests (PFTs) in pts with myositis–associated interstitial lung disease (ILD). Plasma PON1 activity was measured using paraoxon as the substrate and the PON1 Q192R genotype was determined as described previously (A&R 2013,65(11) 2765). Lipoprotein cholesterol levels were assessed by standard assays and traditional CV risk factors and myositis disease characteristics were assessed by questionnaire and chart review.

Results:

PON1 activity was highest in DM patients with the RR genotype, intermediate for the QR genotype, and lowest for the QQ genotype (Table). Pts with the QQ genotype had trends for lower levels of systemic inflammation, higher HDL cholesterol (HDL-C), and significantly lower global disease activity/damage scales compared to QR or RR genotypes (Table). In patients with ILD who had available PFTs (n=30), the % predicted DLCO was significantly higher in the QQ group compared to the QR group; this relationship remained in multivariate (MV) analysis controlling for age and sex. A significant association of the QQ genotype with lower global disease activity (VAS) also remained in MV analysis controlling for demographic characteristics, medication use, disease duration, and HDL-C levels. Higher HDL-C levels were significantly associated with lower disease activity in this analysis.

Conclusion:

In a large cross-sectional cohort of DM pts, the PON1Q192R QQ genotype was associated with a more favorable disease activity profile including lower global disease activity assessments and higher DLCO in patients with myositis-associated ILD. Because DM is a systemic vascular disease and the PONQ192R polymorphism has previously been associated with vascular outcomes, further investigation and validation of these findings is warranted.

QQ Genotype (n=42)

QR Genotype

(n=62)

RR Genotype

(n=14)

PON1 activity (nmoles/minute/ml)

86 ± 61

162 ± 84*

202 ± 103*

Age (years)

49 ± 15

46 ± 14

51 ± 14

Sex (% female)

76

77

78

Race (% caucasian)

93

78

79

Ethnicity (% hispanic)

12

25

36

Body Mass Index (kg/m2)

28 ± 7

28 ± 7

28 ± 5

Disease Duration (years)

5.7 ± 9.3

3.3 ± 6.3

5.8 ± 9.4

Total Cholesterol (mg/dL)

201 ± 38

207 ± 55

197 ± 42

LDL Cholesterol (mg/dL)

115 ± 34

121 ± 47

117 ± 35

HDL Cholesterol (mg/dL)

61 ± 19

56 ± 20

49 ± 15

Triglycerides (mg/dL)

144 ± 81

175 ± 119

171 ± 118

ESR (mm/hr)

24 ± 23

31 ± 28

39 ± 39

HS-CRP (mg/L)

6.2 ± 10.1

6.8 ± 11.1

9.1 ± 13.4

CPK

262 ± 825

409 ± 1097

224 ± 269

Prednisone Use (% yes)

71

70

57

Prednisone daily dose (mg)

14 ± 17

19 ± 20

9 ± 15

Methotrexate (% yes)

29

33

21

Mycophenalate Mofetil (% yes)

25

25

21

Azathioprine (% yes)

18

8

14

IVIG (% yes)

22

23

14

Diabetes (% yes)

10

10

0

Current smoking (% yes)

5

2

0

Hypertension (% yes)

33

18

29

Hydroxychloroquine (% yes)

22

28

21

Physician Global Activity-VAS

34 ± 19

46 ± 18*

39 ± 21

Physician Global Activity-Likert

1.5 ± 0.7

2.0 ± 0.8*

1.7 ± 0.7

Physician Global Damage-VAS

26 ± 21

35 ± 26

37 ± 19*

Physician Global Damage-Likert

1.1 ± 0.9

1.6 ± 1.1*

1.7 ± 0.8*

% of patients with ILD

29

35

79*

FVC % Predicted (in ILD pts)

71 ± 18

60 ± 25

65 ± 19

DLCO % Predicted (in ILD pts)

74 ± 19

49 ± 24*

55 ± 20

*P<0.05 compared to QQ genotype. ESR=erythrocyte sedimentation rate, HSCRP=high sensitivity C-reactive protein, ILD=interstitial lung disease, FVC=forced vital capacity, DLCO=diffusing capacity for carbon monoxide. VAS= Visual analogue scale (0-100 mm scale), Likert= 0-4 scale. PFT data presented for 30 ILD patients with PFTs available (QQ: n=7, QR: n= 13, RR: n= 10).


Disclosure: S. Bae, None; B. Oganesian, None; T. Dowd, None; I. Golub, None; A. Shahbazian, None; J. Wang, None; S. T. Reddy, None; C. Charles-Schoeman, None.

To cite this abstract in AMA style:

Bae S, Oganesian B, Dowd T, Golub I, Shahbazian A, Wang J, Reddy ST, Charles-Schoeman C. Association of the Paraoxonase 1 Q192R Genetic Polymorphism with Disease Activity in Dermatomyositis [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/association-of-the-paraoxonase-1-q192r-genetic-polymorphism-with-disease-activity-in-dermatomyositis/. Accessed .

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