| Abstract | Reumatoidni artritis je kronična, sistemska upalna bolest nepoznatog uzroka. Razlika u prevalenciji i incidenciji RA u različitim etničkim skupinama može se dijelom objasniti različitom učestalošću i tipom alela zajedničkog epitopa HLA-DRB1 gena u pojedinim populacijama, koji su ujedno i čimbenici rizika za teži oblik bolesti. Cilj ovog istraživanja bio je utvrditi prevalenciju RA u SDŽ te istražiti povezanost genetskih i kliničkih obilježja bolesti u pacijenata s RA s područja SK.
Prikupljanje podataka za utvrđivanje prevalencije RA u SDŽ provedeno je uvidom u medicinsku dokumentaciju, pregledom reumatologa i anketnim upitnikom. Provedena je HLA-DRB1 genotipizacija (DRB1*01 - DRB1*16) u 74 RA pacijenta i 80 zdravih ispitanika s područja SK i s područja ostatka SDŽ metodom PCR-SSO te određivanje podtipova HLA-DRB1*04 alela pomoću PCR-SSP. Utvrđivanje težine bolesti provedeno je pregledom reumatologa, određivanjem reaktanata akutne faze, protutijela (RF, anti-CCP), aktivnosti bolesti (DAS28), stupnja funkcionalne sposobnosti (HAQ-Di) i radiološkog oštećenja zglobova (Larsen). Istražene su razlike u povezanosti alela HLA-DRB1 gena s navedenim parametrima između pacijenata s RA s područja SK i pacijenata s područja SDŽ.
Prevalencija RA u SDŽ iznosi 0,24% i veća je u žena (0,39%) nego u muškaraca (0,07%). U pacijenata s RA s područja SK učestalost alela HLA-DRB1*04 značajno je viša nego u pacijenata s RA s područja ostatka SDŽ (18,2% vs 9,5%; P=0,014). Alel HLA-DRB1*15 značajno je više zastupljen u pacijenata s RA s područja ostatka SDŽ nego u pacijenata s područja Sinjske krajine (16,2% vs 7,4%; P=0,010). Nije utvrđena razlika u učestalosti HLA-DRB1*01 alela između oboljelih (P=0,119). Pacijenti s područja SK koji su nositelji alela zajedničkog epitopa češće imaju povišenu vrijednost anti-CCP-a (P=0,014) i RF (P=0,004), jaču aktivnost bolesti (P=0,043), teži do vrlo teški stupanj funkcionalne nesposobnosti (P<0,001) i izraženije radiološke promjene (P=0,003) u odnosu na pacijente nositelje alela zajedničkog epitopa s područja ostatka SDŽ.
Raspodjela i učestalost alela zajedničkog epitopa različita je u pacijenata s RA s područja SK u odnosu na pacijente s područja ostatka SDŽ. Pacijenti s RA s područja SK imaju teži oblik bolesti od pacijenata s područja SDŽ. Povećana učestalost HLA-DRB1*04 alela i podtipova *04:01 i *04:04 u pacijenata s RA s područja SK i niža učestalost u pacijenata s RA s područja ostatka SDŽ mogla bi objasniti navedene razlike u težini bolesti koje su utvrđene u pacijenata s RA s područja Sinjske krajine. |
| Abstract (english) | Rheumatoid arthritis is a chronic, systemic inflammatory disease of unknown cause. The difference in the prevalence and incidence of RA in different ethnic groups can be partly explained by different frequency and type of shared epitope alleles HLA-DRB1 gene in some populations, which are also risk factors for severe forms of the disease. The aim of this study was to evaluate the prevalence of RA in Split-Dalmatia County and to investigate the association of genetic and clinical characteristics of the disease in patients with RA in Sinj region.
The collection of data for determining the prevalence of RA in the Split-Dalmatia County was conducted by examining the medical records, examination of rheumatologists and survey questionnaire. HLA-DRB1 genotyping was performed (DRB1*01 - DRB1*16) by using PCR-SSO in 74 RA patients and 80 healthy subjects from the Sinj region as well as in 74 patients with RA and 80 healthy subjects from the rest of the Split-Dalmatia County. Subtypes of HLA-DRB1*04 alleles were determined by using PCR-SSP. The assessment of the severity of the disease was conducted by rheumatologist’s examination, the determining of acute phase reactants, antibodies (RF and ACPA), disease activity (DAS28), the degree of functional ability (HAQ-DI) and radiological joint damage (Larsen). Differences in association of alleles HLA-DRB1 gene with the specified clinical parameters between RA patients from the Sinj region and RA patients from the rest of the Split-Dalmatia County were investigated.
The prevalence of RA in the Split-Dalmatia County was 0.24% and it was higher among females (0.39%) than males (0.07%). In patients with RA from the Sinj region frequency of HLA-DRB1*04 allele was significantly higher than in patients with RA from the rest of the Split-Dalmatia County (18.2% vs 9.5%; P=0.014). Allele HLA-DRB1*15 was significantly more prevalent in patients with RA from the rest of the Split-Dalmatia County than in patients from the Sinj region (16.2% vs 7.4%; P=0.010). There was no difference in the frequency of HLA-DRB1*01 allele between patients (P=0.119).
The frequency of ACPA and RF antibodies was higher in shared epitope (SE) positive patients from the Sinj region compared with the SE-positive patients from the rest of the Split-Dalmatia County (P=0.014, and P=0.004, respectively). SE-positive patients from the Sinj region had stronger activity of the disease (P=0.043), more severe degree of functional disability (P<0.001) and more severe radiological changes (P=0.003), compared with the SE-positive patients from the rest of the Split-Dalmatia County. |
