Analysis of the Association of PTGER4 Gene Variants with Radiological Joint Damage in Rheumatoid Arthritis

Luis Rodriguez-Rodriguez^1,2, J. Ivorra-Cortes³, Francisco David Carmona⁴, Javier Martín⁵, Alejandro Balsa⁶, H.W. van Steenbergen⁷, A. H. M. van der Helm- van Mil⁸, Isidoro González-Alvaro⁹ and Benjamín Fernández-Gutiérrez¹⁰, ¹Instituto de Investigación Sanitaria San Carlos (IdISSC), Madrid, Spain, ²Hospital Clínico San Carlos, Department of Rheumatology, Madrid, Spain, ³Rheumatology, University Hospital la Fe, Valencia, Spain, ⁴Instituto de Parasitología y Biomedicina López-Neyra, IPBLN-CSIC, PTS-Granada, Granada, Spain, ⁵Instituto de Parasitología y Biomedicina López- Neyra, IPBLN-CSIC, PTS-Granada, Granada, Spain, ⁶Rheumatology, La Paz University Hospital-Rheumatology Department, Madrid, Spain, ⁷Leiden University Medical Center, Leiden, Netherlands, ⁸Rheumatology, Leiden University Medical Center, Leiden, Netherlands, ⁹Rheumatology Department, Hospital Universitario la Princesa, IIS-Princesa, Madrid, Spain, ¹⁰Department of Rheumatology, Hospital Clínico San Carlos, Madrid, Spain

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: joint damage, polymorphism and rheumatoid arthritis (RA)

Session Information

Date: Sunday, November 8, 2015

Title: Genetics, Genomics and Proteomics Poster I

Session Type: ACR Poster Session A

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

Background/Purpose: PTGER4(prostaglandin E receptor 4) is implicated in immune regulation and bone metabolism. The aim of this study was to analyze the role of single nucleotide polymorphisms (SNPs) located in this locus in radiological joint damage in rheumatoid arthritis (RA).

Methods: 6 independent cohorts of RA patients of European and North-American descent were included in this study, comprising 1,789 patients with 5,083 sets of X-rays. Three cohorts from Madrid (Spain) were used for identification: Hospital Clínico San Carlos Rheumatoid Arthritis Cohort, the Hospital Universitario de la Princesa Early Arthritis Register Longitudinal cohort, and the Hospital Universitario de La Paz early arthritis cohort. On the other hand, the Leiden Early Arthritis Clinic Cohort (The Netherlands), Wichita (US) and National DataBank (US and Canada) cohorts were used for replication. First, the PTGER4 rs6896969 SNP was genotyped using Taqman assays and available Illumina Immunochip data. The latter was also used to obtain genotyping data from the PTGER4 gene and adjacent regions (Chr 5: from 38,957,820 bp to 41,336,050 bp; GRCh37/hg19). The effect of the SNPs on radiological joint damage was assessed using two models: a continuous effect model that analyzes the overall effect of each SNP in radiological damage, assuming a stable effect over time, and a time-varying effect model that analyzes the effect of the SNP in the slope (progression) of the radiological damage. Linkage disequilibrium (LD) structure of the locus was assessed and for each LD block (r²>0.9), 1 SNP with a p value <0.05, preferably located in a region with transcriptional properties, was selected for replication. Results from the different cohorts were pooled using inverse variance-weighted meta-analysis, and the pooled p values were adjusted using the Bonferroni method, based on the number of effectively independent SNPs tested, and in the fact that we performed a continuous and a time-varying effect analysis for each SNP (threshold p value=1.3×10^-4).

Results: The rs6896969 polymorphism showed a significant association with radiological damage in the continuous effect pooled analysis of the Spanish cohorts, although no significant association was observed in the replication cohorts or when the results from the 6 cohorts were pooled. In the analysis of the PTGER4 region, 12 and 20 SNPs, from the continuous and time-varying effect models, respectively, were analyzed in the replication cohorts. Only the rs76523431 variant showed a significant association with higher radiographic progression in the time-varying effect analysis (overall pooled p=2.10×10^-5, I²=0.13).

Conclusion: The PTGER4 gene could play a role in RA radiological progression.

Disclosure: L. Rodriguez-Rodriguez, None; J. Ivorra-Cortes, None; F. D. Carmona, None; J. Martín, None; A. Balsa, None; H. W. van Steenbergen, None; A. H. M. van der Helm- van Mil, None; I. González-Alvaro, None; B. Fernández-Gutiérrez, None.

To cite this abstract in AMA style:

Rodriguez-Rodriguez L, Ivorra-Cortes J, Carmona FD, Martín J, Balsa A, van Steenbergen HW, van der Helm- van Mil AHM, González-Alvaro I, Fernández-Gutiérrez B. Analysis of the Association of PTGER4 Gene Variants with Radiological Joint Damage in Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/analysis-of-the-association-of-ptger4-gene-variants-with-radiological-joint-damage-in-rheumatoid-arthritis/. Accessed .

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