POLYMORPHISM OF SEROTONIN RECEPTOR (5-HTR2A) GENE AND ITS INFLUENCE ON THERAPEUTIC EFFICACY IN PATIENTS WITH RHEUMATIC ARTHRITIS

Rheumatoid arthritis (RA) is a chronic, systemic and infammatory disorder of unknown aetiology that primarily involves bodily joints. Serotonin (5-HT) is a key neurotransmitter in the central nervous system. It is suggested that serotonergic dysfunction may be involved in the pathophysiology of RA. We also saw that patients with the T/T genotype had the lowest pain threshold. The purpose of research was study the effectiveness of treatment in patients with Rheumatic Arthritis according with Different Variants of Polymorphic Sites of Serotonin Receptor 5-HTR2A T102S or A-1438 — G Gene.

Material and methods: the distribution of genotype rate of serotonin receptor 5-HTR2A

T102C or A-1438-G gene was studied in 100 patients with RA. Polymorphic areas of T102C or A-1438-G gene were amplified with polymerase chain reaction. Anxiety level was assessed by Spielberger State-Trait Anxiety Scale. Depressive status and depression severity was evaluated by Hamilton Depression Rating Scale. Рain intensity was determined by 100 мм visual analogue scale. The state of functional competence in patients with RA was studied using the Stanford Health Assessment Questionnaire (HAQ). Аssessment of RA activity by means of integral and clinical indices of disease activity scale by DAS28, CDAI і SDAI. Statistical data processing was done with Statistical package for Windows v. 8.0 using parametric and nonparametric methods. Differences between comparable parameters were considered significant if confidence value was 95 % (p<0.05).

Results and discussion. Study of dynamics of such indices as number of painful and swollen joints, indices of inflammatory process by DAS28, CDAI, SDAI, pain intensity by VAS as well as indices of anxiety depressive disorders after three months of treatment demonstrated that among the patients with TT genotype improvement of state by ACR criteria by 20% occurred in 21.4% of patients and by 50% — in 3.6%; in patients with TC genotype improvement by 20% occurred in 22.6%, by 50% — in 3.8%, while 41.1% of patients with СС genotype had 20% response to therapy,15.8% of patients had 50% improvement and 5.3% had 70% improvement. It was found that in patients with AG genotype after three months of treatment improvement of state by ACR criteria by 20% occurred in 44.7%, by 50% — in 10.6% of patients, while among the patients with GG genotype 44.4% of patients responded to therapy by 20%, 11.1% of patients — by 50%. Among the patients with АА genotype 47.0% of responders had ACR 20, by ACR 50 — 11.8%, by ACR 70 — 5.9%.

Conclusions. The most positive dynamics in the studied indices after three months of treatment were noted in patients with CC genotype of T102C locus and AA locus A-1438-G gene as among them there was the greatest number of respondents by ACR 20, ACR 50 and ACR 70. Thus, the efficacy of therapy in patients with RA depends on the variant of polymorphic sites of promotor region of 5-HTR2A gene, and T allele is a predictor of resistance to treatment.