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AB0264 STAT4 RS7574865 Gene Polymorphism is not Associated with Severe Disease Phenotype and Response to Tumor Necrosis Factor-α Inhibitor Treatment in Patients with Rheumatoid Arthritis
  1. G. Ozen1,
  2. B. Saglam2,
  3. A. Odabasi2,
  4. O. Ozluk2,
  5. S.P. Yentur3,
  6. G. Saruhan-Direskeneli3,
  7. N. Inanc1,
  8. H. Direskeneli1
  1. 1Rheumatology
  2. 2Internal Medicine, Marmara University School of Medicine
  3. 3Physiology, Istanbul University Istanbul Faculty of Medicine, Istanbul, Turkey

Abstract

Objectives To investigate the association between single nucleotide polymorphism (SNP) of rs7574865 in signal transducer and activator of transcription 4 (STAT4) gene and RA susceptibility among the Turkish population and to determine the effects of this genetic variant on disease characteristics and response to tumor-necrosis factor-α inhibitor (TNFi) treatment.

Methods rs7574865 SNP of STAT4 was genotyped in a total of 389 Turkish RA patients fulfilling the 1987 ACR classification criteria (F/M: 324/65, mean age: 52.8±12.6 years, 66.8% RF positive) and 573 healthy controls (F/M: 248/275, mean age: 30.1±9.9 years). Retrospectively, along with disease characteristics, EULAR response to biologic DMARDs, especially TNFi, DAS28 scores of each visit during the entire follow-up of RA patients (complete disease activity data were obtained from 318 patients) were recorded.

Results The genotype distribution showed that RA cohort (GG: 297 [76.3%], GT: 79 [20.4%], TT: 13 [3.3%] patients) had significantly higher rate of TT genotype compared to HC (GG:431 [82.4%], GT:84 [16.1%], TT: 8 [1.5%] individuals) (P=0.04). Presence of T minor allele (GT or TT genotype) was also significantly higher in RA patients (23.7% vs 17.6%, OR=1.44; CI:95% 1.042-1.99, P=0.03). However, T allele carrier rates of seronegative (16.9%) and seropositive (25.6%) (either RF or Anti-CCP) patients were similar (P=0.14). Biologic treatment requirements, extra-articular involvement and joint surgery rates were similar in RA patients with and without T allele (Table 1). During 6.0±4.0 years follow-up period, in a median of 10 (min-max: 2-42) visits, the ratio of visits in moderate-high disease activity and remission-low disease activity and sustained remission rate (remission in 3 consecutive visits) were not different in patients with and without T allele (Figure 1). Of the 161 patients treated with biologic DMARDs, 141 received TNFi (infliximab 51, adalimumab 47, etanercept 43 patients) and the EULAR response to TNFi at 6th month were also similar in T allele carrier and non-carrier patients (59.3% vs 71.9%, P=0.19). Seropositivity for either RF or anti-CCP (82.4% vs 80.5%), disease durations (13.9 vs 14.3 years) and baseline DAS28 scores (5.34 vs 5.31) were also comparable in TNFi responders and nonresponders.

Table 1.

Disease characteristics of RA patients according to presence of T allele in STAT4 rs7574865 SNP

Conclusions The data revealed that T allele of STAT4 rs7574865 was associated with an increased risk of RA in Turkish population. However presence of T allele does not seem to have an effect on disease phenotype and TNFi response.

Disclosure of Interest None declared

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