SE Elméleti Orvostudományi Központ, Hári terem I. em.
2023-06-07 13:00:00
Elméleti és klinikai immunológia
Dr. Poór Gyula
Dr. Poór Gyula
Dr. Szántó Sándor
Dr. Mészáros Szilvia
Dr. Csala Miklós
Dr. Ábrahám György
Dr. Takács István
Gout is a common crystal induced disease with high personal and social burden. It is characterised by severe arthritis and comorbidities, if left untreated. ABCG2 urate transporter dysfunction is known to be strongly related to gout and lately it was also connected with renal-overload type hyperuricemia. However, despite being a key factor, our information is still limited on how ABCG2 genetic changes in gouty patients relate to protein expression and that to clinical parameters.
This thesis synthesises existing literature and our previous results concerning 78 gouty patients and 73 healthy controls from a Hungarian population. ABCG2 protein expression was measured on red blood cells by a flow cytometry-based method, while genetic background was determined by TaqMan-based qPCR. All urate and clinical parameters were determined among standardised circumstances.
The prevalence of ABCG2 mutations in gouty and control patients were 32.1% and 13.7%, respectively. Most common SNP was Q141K while one sample with R236X and with R383C was found. We firstly described a new M71V functional mutation that results in an active but structurally unstable protein. These ABCG2 mutations showed strong association with impaired protein expression, while this disfunction was associated with higher disease severity and significantly elevated clinical indices of fractional urate excretion (FUE) and urinary urate excretion (UUE) compared to wild type gouty patients.
This thesis highlights the significance of the ABCG2 urate transporter in gout. It manages to firstly evaluate ABCG2 protein expression in a clinically defined gouty population while also proving its association between already known, and newly described ABCG2 genetic mutations and renal-overload hyperuricemia. The thesis also assesses relations between ABCG2 mutations, gout susceptibility and disease severity characterised by early onset disease with frequent flares and tophi formation. The study was registered by the Scientific and Research Ethic Committee of the Medical Research Council, Hungary (41006-1/2013/EKU).
