| Abstract | Primarni osteoartritis (POA) predstavlja najčešću bolest koštano-zglobnog sustava. Dio rizika se nasljeđuje poligenski, a zahvaća ljude starije životne dobi. Etiologija ove bolesti nije u potpunosti razjašnjena. Cilj istraživanja je ispitati povezanost točkastkih polimorfizama gena interleukina -17 (IL17A i IL17F) i Toll-nalik receptor 10 (TLR10) s predispozicijom za nastanak POA koljena i kuka u hrvatskoj populaciji ispitanika s uznapredovalim stadijem ove bolesti. Genotipizirano je 500 bolesnika s POA i 597 kontrola na gene IL17A SNP (rs2275913), IL17F SNP (rs763780 i rs1889570) i TLR10 (rs11096957). Statistički značajna razlika se pronašla u frekvencijama alela i genotipova IL17F SNP (rs763780) pri uspoređivanju kontrolne skupine i bolesnika s POA kuka, ali ne i koljena. Pronađena je povezanost visokofrekventnog alela (T) rs763780 s niskim rizikom razvoja POA kuka (p=7,9x10-4, OR=0,45, CI 95%=0,27-0,74), dok je manjefrekventni alel (C) povezan s predispozicijom za razvoj POA kuka (p=7,9x10-4, OR=2,24, CI 95%=1,35-3,72). Genotip T/T je povezan sa zaštitom od razvoja POA kuka (p=3,9x10-4, OR=0,41, CI 95%=0,24-0,70), a genotip T/C je povezan s povećanim rizikom za razvoj POA kuka (p=2,6x10-4, OR=2,50, CI 95%=1,47-4,25). Pronađena je statistički značajna povezanost TLR10 SNP (rs11096957) s predispozicijom za razvoj POA kuka (p=0,04, OR=1,41, CI 95%=1,02-1,94), ali ne i za POA koljena. Analizom haplotipa s tri markera (IL17A - IL17F - IL17F’) G-C-A potvrđuje se predispozicija za razvoj POA kuka, ali ne i POA koljena. Povećan rizik za razvoj POA koljena nađen je povezan samo s A-T-G haplotipom. Rezultati haplotipske analize s dva markera (IL17A - IL17F i IL17F - IL17F’) su pokazali povezanost s predispozicijom za razvoj POA kuka sa 4 puta većim rizikom za razvoj bolesti kod osoba s G-C IL17A - IL17F haplotipom (p=0,43x10-4). Međutim, analiza haplotipa G-T (IL17A-IL17F) pokazala je moguću povezanost sa zaštitnom ulogom kod razvoja POA kuka (p=6x10-4). Rezultati istraživanja IL17 i TLR10 gena u hrvatskoj populaciji ukazuju na potencijalno različiti genetski rizik razvoja POA kuka i koljena. |
| Abstract (english) | Primary osteoarthritis (POA) is the most common type of joint disease. It has a polygenic inheritance pattern and primarily affects older people. The etiology of this disease is not fully understood. The aim of this study was to investigate the associations between polymorphisms in pro-inflammatory interleukin-17 (IL17A and IL17F) and anti-inflammatory Toll-like Receptor 10 (TLR10) genes and the risk of development of advanced hip and knee POA in the Croatian population. A total of 500 POA patients and 597 controls were genotyped for IL17A SNP (rs2275913), IL17F SNPs (rs763780 and rs1889570), and TLR10 (rs11096957) genes. The allelic and genotypic frequencies of IL17F SNP (rs763780) showed statistically significant differences in comparison with controls, for hip but not knee POA patients. The major allele (T) of rs763780 was associated with a reduced susceptibility to developing hip POA (p=7.9x10-4, OR=0.45, CI 95%=0.27-0.74), whereas the minor allele (C) was associated with an increased susceptibility to hip POA (p=7.9x10-4, OR=2.24, CI 95%=1.35-3.72). The genotype T/T was associated with a lower risk of developing hip POA (p=3.9x10-4, OR=0.41, CI 95%=0.24-0.70), whereas the genotype T/C was associated with a higher risk of developing hip POA (p=2.6x10-4, OR=2.50, CI 95%=1.47-4.25). TLR10 SNP rs11096957 was associated with a significant predisposition to hip POA (p=0.04, OR=1.41, CI 95%=1.02-1.94) but not knee POA. The three-marker haplotype (IL17A-IL17F-IL17F5’) G-C-A confers susceptibility to hip, but not knee POA. The increased risk of developing knee POA was found to be associated only with the A-T-G haplotype. The two-marker haplotypes’ analyses (IL17A-IL17F or IL17F-IL17F5’) showed association only with hip POA, with about 4-fold higher risk for development of the disease in those individuals harboring G-C of the IL17A-IL17F haplotype (p=0,43x10-4). In addition, the haplotype G-T (IL17A-IL17F) is associated with protection to the disease in hip POA (p=6x10-4). The current findings suggest, that amongst the Croatian population, there may be a variable genetic risk profile for developing hip POA, depending on specific IL17 and TLR10 gene loci. This effect, relating to the genes studied, does not appear to influence the development of knee POA in Croatian population. |
