ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 980

Association of Platelet Endothelial Cell Adhesion Molecule-1 and ß1 Integrin Gene Polymorphisms with Uveitis Development in Ankylosing Spondylitis

Seung-Cheol Shim1, In-Seol Yoo2, Su-Jin Yoo1, Young Kim1, Mi-Kyoung Lim3, Dong-Hyuk Sheen4 and Jinhyun Kim5, 1Rheumatology, Chungnam National University School of Medicine, Daejeon, South Korea, 2Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, South Korea, 3Medicine, Eulji University Hospital, Daejeon, South Korea, 4Rheumatology, Eulji University Hospital, Daejeon, South Korea, 5Internal 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: Sunday, November 8, 2015

Title: Spondylarthropathies Psoriatic Arthritis - Pathogenesis, Etiology

Session Type: ACR Concurrent Abstract Session

Session Time: 2:30PM-4:00PM

Background/Purpose:

Genetic factors provide over 90% of the overall susceptibility to ankylosing spondylitis (AS) and recent studies have focused on non-major histocompatibility complex genes. The etiology of uveitis in AS has been suggested to involve two adhesion molecules including intercellular adhesion molecule (ICAM)-1 and leukocyte functional antigen (LFA)-1.

Platelet-endothelial cell adhesion molecule 1 (PECAM1) is a member of the immunoglobulin superfamily which is expressed on endothelial cells. There is emerging evidence that PECAM1 may be an important regulator of activation of lymphocytes. The β1 integrin (ITGB1) can associate with different membrane proteins and cause signal transduction by interactions in the extracellular and trans-membrane domain. Therefore, we examined the association of PECAM1 and ITGB1 gene polymorphisms with development of uveitis in patients with AS.

Methods:

We conducted a case–control study where 223 AS patients who met the Modified New York criteria and 239 ethnically matched controls were genotyped for 9 single nucleotide polymorphisms (SNPs) in the PECAM-1 promoter and gene. Genomic DNA was isolated from peripheral blood leukocytes by a standard phenol–chloroform method and a GoldenGate assay (Illumina, http://www.illumina.com) was used for genotyping.

Results:

Conditional logistic regression was used to evaluate the association between the PECAM1 or ITGB1 SNPs with susceptibility to AS, and no significant association was found on both genes. However, in the subgroup analyses between AS patients with uveitis and those without, seven SNPs in PECAM1 gene were associated with the presence of uveitis, including rs1050382 (dominant model (DM), p=0.022), rs2812 (recessive model (RM), p=0.013), rs4968721 (DM, p=0.016), rs6808 (DM, p=0.011), rs6809 (DM, p=0.013), rs9899806 (DM, p=0.013) and rs9913080 (DM, p=0.019). In addition, seven polymorphisms in ITGB1 gene including rs11009147 (DM, p=0.012; co-dominant model (CDM), p=0.034), rs17468 (DM, p=0.012; CDM, p= 0.019), rs2153875 (CDM, p= 0.030), rs2230396 (DM, p=0.012), rs2488330 (DM, p=0.004), rs3780871 (DM, p=0.031) and rs7079624 (RM, p=0.004) were associated with uveitis development.

Conclusion:

This is the first analysis of the PECAM1 and ITGB1 gene polymorphisms in AS, demonstrating a clear association with uveitis in AS. Larger studies are warranted to elucidate the association of PECAM-1 and ITGB1 in the pathogenesis of uveitis in AS.

Table 1. Logistic analysis of PECAM1 polymorphisms and the risk of uveitis among AS patients

 

rs No.

Dominant Model

Recessive Model

Co-dominant Model

Odds

(95% CI)

P.Value

(adj.P.)

Odds

(95% CI)

P.Value

(adj.P.)

Odds

(95% CI)

P.Value

(adj.P.)

rs1050382

2.170

(1.116-4.219)

0.022

(0.027)

0.456

(0.129-1.611)

0.223

(0.262)

1.314

(0.824-2.095)

0.250

(0.294)

rs11079538

1.623

(0.745-3.537)

0.222

(0.261)

1.289

(0.568-2.924)

0.543

(0.571)

1.345

(0.821-2.202)

0.238

(0.297)

rs2812

2.190

(0.620-7.736)

0.223

(0.247)

0.424

(0.215-0.837)

0.013

(0.024)

0.732

(0.457-1.173)

0.195

(0.300)

rs4968721

2.302

(1.167-4.541)

0.016

(0.022)

0.412

(0.117-1.446)

0.166

(0.237)

1.304

(0.820-2.075)

0.261

(0.290)

rs6808

2.406

(1.220-4.743)

0.011

(0.020)

0.456

(0.129-1.611)

0.223

(0.278)

1.379

(0.862-2.205)

0.178

(0.298)

rs6809

2.354

(1.193-4.641)

0.013

(0.020)

0.456

(0.129-1.611)

0.223

(0.297)

1.364

(0.852-2.184)

0.195

(0.279)

rs8065316

1.124

(0.490-2.578)

0.781

(0.822)

1.774

(0.908-3.468)

0.093

(0.155)

1.360

(0.848-2.180)

0.201

(0.268)

rs9899806

2.354

(1.193-4.641)

0.013

(0.022)

0.509

(0.143-1.813)

0.297

(0.330)

1.414

(0.876-2.283)

0.155

(0.282)

rs9913080

2.252

(1.141-4.443)

0.019

(0.025)

0.392

(0.112-1.373)

0.143

(0.220)

1.270

(0.800-2.016)

0.310

(0.326)

Table 2. Logistic analysis of ITGB1 polymorphisms and the risk of uveitis among AS patients

 

rs number

Dominant Model

Recessive Model

Co-dominant Model

Odds

(95% CI)

P.Value

(adj.P.)

Odds

(95% CI)

P.Value

(adj.P.)

Odds

(95% CI)

P.Value

(adj.P.)

rs11009147

0.436

(0.226-0.839)

0.012

(0.021)

0.712

(0.273-1.858)

0.488

(0.596)

0.582

(0.353-0.960)

0.034

(0.046)

rs1187078

0.873

(0.261-2.921)

0.826

(0.865)

0.919

(0.486-1.737)

0.796

(0.834)

0.926

(0.560-1.532)

0.767

(0.804)

rs17468

0.436

(0.226-0.839)

0.012

(0.019)

0.563

(0.249-1.272)

0.167

(0.245)

0.589

(0.377-0.918)

0.019

(0.030)

rs2153875

0.527

(0.249-1.117)

0.094

(0.122)

0.465

(0.202-1.071)

0.072

(0.113)

0.582

(0.356-0.949)

0.030

(0.044)

rs2230396

0.436

(0.226-0.839)

0.012

(0.020)

0.712

(0.273-1.858)

0.488

(0.565)

0.582

(0.353-0.960)

0.034

(0.044)

rs2298141

1.340

(0.702-2.559)

0.374

(0.457)

3.718

(1.126-12.28)

0.031

(0.052)

1.508

(0.906-2.511)

0.113

(0.131)

rs2488330

0.390

(0.203-0.748)

0.004

(0.008)

0.712

(0.273-1.858)

0.488

(0.631)

0.546

(0.330-0.901)

0.017

(0.032)

rs2503997

1.278

(0.659-2.477)

0.466

(0.540)

1.308

(0.586-2.920)

0.511

(0.562)

1.205

(0.778-1.865)

0.401

(0.441)

rs3780871

0.268

(0.081-0.888)

0.031

(0.042)

0.745

(0.390-1.424)

0.374

(0.514)

0.662

(0.398-1.103)

0.113

(0.139)

rs7079624

1.403

(0.538-3.662)

0.488

(0.536)

2.560

(1.335-4.909)

0.004

(0.008)

1.830

(1.109-3.021)

0.017

(0.030)

Disclosure: S. C. Shim, None; I. S. Yoo, None; S. J. Yoo, None; Y. Kim, None; M. K. Lim, None; D. H. Sheen, None; J. Kim, None.

To cite this abstract in AMA style:

Shim SC, Yoo IS, Yoo SJ, Kim Y, Lim MK, Sheen DH, Kim J. Association of Platelet Endothelial Cell Adhesion Molecule-1 and ß1 Integrin Gene Polymorphisms with Uveitis Development in Ankylosing Spondylitis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/association-of-platelet-endothelial-cell-adhesion-molecule-1-and-s1-integrin-gene-polymorphisms-with-uveitis-development-in-ankylosing-spondylitis/. Accessed .

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