ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1612

Association of Single Nucleotide Polymorphisms of PADI4 and HLA-DRB1 Alleles with Susceptibility to Rheumatoid Arthritis-Related Lung Diseases

Seung-Cheol Shim1, In-Seol Yoo2, Su-Jin Yoo1, Young Kim1, Jinhyun Kim3 and Seong-Wook Kang2, 1Rheumatology, Chungnam National University School of Medicine, Daejeon, South Korea, 2Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, South Korea, 3Internal medicine, Chungnam National University School of Medicine, Daejeon, South Korea

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: ,

Session Information

Date: Monday, November 9, 2015

Title: Rheumatoid Arthritis - Human Etiology and Pathogenesis Poster II

Session Type: ACR Poster Session B

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

Background/Purpose:

Lung diseases (LD) are common extra-articular manifestations in rheumatoid arthritis (RA). Recent studies have shown the association of RA-LD with anti-citrullinated protein antibodies. The peptidylarginine deiminase (PADI) mediates post-translational deimination of peptidylarginine to a non-standard amino acid peptidylcitrulline.

The aim of the present study was to investigate whether the single nucleotide polymorphisms (SNPs) of PADI4 are associated with RA-LD.

Methods:

Blood samples and clinical data were collected from 116 consecutive RA patients who satisfied the 1987 American College of Rheumatology classification criteria. RA-LD was diagnosed using high-resolution computed tomography of the chest and a pulmonary function test. All of the patients were genotyped for SNPs of PADI4 and HLA-DRB1 alleles. The independent t-test or Mann-Whitney test for continuous variables, the chi-square test or Fisher’s exact test for categorical variables, and multivariate logistic regression analysis to assess genetic susceptibility to RA-LD were performed.

Results:

Of the 103 RA patients, 8 (7.8%) had interstitial lung disease (ILD) and 33 (32.0%) had small airway disease (AD). High titers of ACPA (≥80 U/mL; p=0.022) and RF (≥ULN×3; p=0.008) were significantly associated with susceptibility to RA-LD. The minor allele homozygote of padi4_92 was susceptible to RA-large AD (OR = 3.11 , 95% CI = 1.29-7.48). The recessive genotypes of padi4_89 (OR = 3.69, 95% CI = 1.14-11.95) and padi4_104 (OR = 3.47, 95% CI = 1.10-11.00) were susceptible to large AD. HLA-DRB1 *0405 was protective against the development of RA-AD (OR = 0.32, 95% CI = 0.11-0.98). The combination of any HLA-DRB1 *04 alleles except the *0405 and padi4_92 GG+ presented a synergistic effect on the development of RA-large AD (OR = 17.73, 95% CI = 2.22-141.63).

Conclusion:

This study demonstrates the association of SNPs of PADI4and HLA-DRB1 alleles with susceptibility to RA-LD.

Table 1. Association of the SNPs of PADI4with the development of each pattern of lung diseases.

SNP

Allele

RA-no LD

(n = 16)

RA-ILD

(n = 8)

OR

(95% CI)

RA-Large AD

(n = 63)

OR

(95% CI)

RA-Small AD

(n = 6)

OR

(95% CI)

RA- CombinedAD

(n = 23)

OR

(95% CI)

padi4_89

 

 

 

 

 

 

A

0.625

0.500

1

0.476

1

0.667

1

0.609

1

G

0.375

0.500

0.71 (0.05-10.21)

0.524

1.85 (0.82-4.18)

0.333

0.68 (0.16-2.91)

0.391

0.84 (0.29-2.41)

padi4_92

 

 

 

 

 

 

C

0.375

0.375

1

0.151

1

0.500

1

0.348

1

G

0.625

0.625

0.32 (0.03-3.42)

0.849

3.11 (1.29-7.48)

0.500

0.53 (0.13-2.13)

0.652

1.04 (0.36-3.00)

padi4_104

 

 

 

 

 

 

C

0.656

0.562

1

0.587

1

0.833

1

0.630

1

T

0.344

0.438

0.13 (0.004-4.17)

0.413

1.27 (0.56-2.90)

0.167

0.30 (0.05-1.75)

0.370

0.90 (0.31-2.62)

Table 2. Association of genotypes of PADI4with the development of each pattern of lung diseases.

SNP

Genotype

RA-no LD

(n = 16)

RA-ILD

(n = 8)

OR

(95% CI)

RA-Large AD

(n = 63)

OR

(95% CI)

RA-Small AD

(n = 6)

OR

(95% CI)

RA- CombinedAD

(n = 23)

OR

(95% CI)

padi4_89

 

 

 

 

 

 

AA

8 (50.0)

3 (37.5)

1

13 (20.6)

1

3 (50.0)

1

8 (34.8)

1

AG+GG

8 (50.0)

5 (62.5)

0.74 (0.07-7.85)

50 (79.4)

3.69 (1.14-11.95)

3 (50.0)

0.75 (0.10-5.60)

15 (62.5)

1.57 (0.36-6.79)

AG

5 (31.3)

2 (25.0)

1

34 (54.0)

1

2 (33.3)

1

12 (52.2)

1

AA+GG

11 (68.8)

6 (75.0)

1.02 (0.11-9.51)

29 ((46.0)

0.41 (0.12-1.33)

4 (66.7)

1.00 (0.13-7.77)

11 (47.8)

0.32 (0.07-1.52)

AA+AG

13 (81.2)

6 (75.0)

1

47 (74.6)

1

5 (83.3)

1

20 (87.0)

1

GG

3 (18.8)

2 (25.0)

0.71 (0.05-10.21)

16 (25.4)

1.56 (0.38-6.41)

1 (16.7)

0.64 (0.05-8.54)

3 (13.0)

0.26 (0.03-2.16)

padi4_92

 

 

 

 

 

 

CC

4 (25.0)

3 (37.5)

1

7 (11.1)

1

2 (33.3)

1

8 (34.8)

1

CG+GG

12 (75.0)

5 (62.5)

8.85 (0.64-123.30)

56 (88.9)

2.31 (0.58-9.21)

4 (66.7)

0.65 (0.08-5.29)

15 (65.2)

0.65 (0.13-3.17)

CG

4 (25.0)

0 (0.0)

1

5 (7.9)

1

2 (33.3)

1

0 (0.0)

1

CC+GG

12 (75.0)

8 (100.0)

7.09 (0.11-455.14)

58 (92.1)

4.37 (0.95-20.15)

4 (66.7)

0.50 (0.06-4.47)

23 (100.0)

0.06 (0.001-2.37)

CC+CG

8 (50.0)

3 (37.5)

1

12 (19.0)

1

4 (66.7)

1

8 (34.8)

1

GG

8 (50.0)

5 (62.5)

0.32 (0.03-3.42)

51 (81.0)

4.07 (1.25-13.30)

2 (33.3)

0.39 (0.05-3.11)

15 (65.2)

1.57 (0.36-6.79)

padi4_104

 

 

 

 

 

 

CC

9 (56.2)

3 (37.5)

1

17 (27.0)

1

4 (66.7)

1

9 (39.1)

1

CT+TT

7 (43.8)

5 (62.5)

0.55 (0.06-5.11)

46 (73.0)

3.47 (1.10-11.00)

2 (33.3)

0.57 (0.08-4.34)

14 (60.9)

2.01 (0.46-8.76)

CT

3 (18.8)

3 (37.5)

1

39 (61.9)

1

2 (33.3)

1

11 (47.8)

1

CC+TT

13 (81.3)

5 (62.5)

0.36 (0.04-3.65)

24 (38.1)

0.13 (0.03-0.51)

4 (66.7)

0.38 (0.04-3.54)

12 (52.2)

0.10 (0.01-0.95)

CC+CT

12 (75.0)

5 (62.5)

1

57 90.5)

1

6 (100.0)

1

20 (87.0)

1

TT

4 (25.0)

3 (37.5)

0.13 (0.004-4.17)

6 (9.5)

0.23 (0.05-1.05)

0 (0.0)

0.06 (0.001-6.60)

3 (13.0)

0.23 (0.04-1.52)

Table 3. Combined effects of HLA-DRB1 *0405 allele and padi4_92 genotype on the development of each pattern of lung diseases.

 

RA-no LD

(n = 16)

RA-ILD

(n = 8)

OR

(95% CI)

RA-Large AD

(n = 63)

missing = 1

OR

(95% CI)

RA-Small AD

(n = 6)

OR

(95% CI)

RA- Combined AD

(n = 23)

OR

(95% CI)

RA-AD

(n = 92)

missing = 1

OR

(95% CI)

RA-LD

(n = 100)

missing = 1

OR

(95% CI)

*0405+/padi4_92GG-

4 (25.0)

2 (25.0)

1

3 (4.8)

1

1 (16.7)

1

1 (4.3)

1

5 (5.5)

1

7 (7.1)

1

*0405+/padi4_92GG+

6 (37.5)

1 (12.5)

0.25

(0.01-4.69)

19 (30.6)

3.95

(0.68-23.01)

0 (0.0)

0.18

(0.004-7.75)

7 (30.4)

2.99

(0.21-42.94)

26 (28.6)

3.31

(0.65-16.81)

27 (27.3)

2.61

(0.55-12.39)

*0405-/padi4_92GG-

4 (25.0)

1 (12.5)

0.91

(0.04-21.33)

9 (14.5)

2.63

(0.38-17.98)

3 (50.0)

2.56

(0.22-29.47)

7 (30.4)

5.14

(3.41-77.67)

19 (20.9)

3.37

(0.60-19.12)

20 (20.2)

2.78

(0.52-14.78)

*0405-/padi4_92GG+

2 (12.5)

4 (50.0)

0.44

(0.02-10.44)

31 (50.0)

17.73

(2.22-141.63)

2 (33.3)

2.59

(0.17-38.75)

8 (34.8)

11.45

(0.64-205.69)

41 (45.1)

15.76

(2.20-112.96)

45 (45.5)

12.32

(1.81-83.98)

Disclosure: S. C. Shim, None; I. S. Yoo, None; S. J. Yoo, None; Y. Kim, None; J. Kim, None; S. W. Kang, None.

To cite this abstract in AMA style:

Shim SC, Yoo IS, Yoo SJ, Kim Y, Kim J, Kang SW. Association of Single Nucleotide Polymorphisms of PADI4 and HLA-DRB1 Alleles with Susceptibility to Rheumatoid Arthritis-Related Lung Diseases [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/association-of-single-nucleotide-polymorphisms-of-padi4-and-hla-drb1-alleles-with-susceptibility-to-rheumatoid-arthritis-related-lung-diseases/. Accessed .

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