Genetic Aspects of Rheumatoid Arthritis. Summary of the Doctoral Thesis

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory destructive joints disease with essential personal, social and economic impact. Differences between ethnic groups in susceptibility to RA, disease heterogeneity and variations in clinical, radiological and laboratory findings suggest that several factors influence the occurrence and progression of RA. The genetic component has a large impact. The aim of the study was to investigate the association of genetic factors on manifestations of RA in Latvian population. Doctoral thesis summarizes the data about RA patients. Be defined stages of the disease, activity and severity of disease according to current evaluation criteria. This is the first time genotyping was performed in Latvia for population of patients with RA for PTPN22 gene (rs2476601), KLF12 gene (rs1324913), TNFA gene promoter -308 position (rs1800629), IL6 gene promoter position -174 (rs1800795), IL18 gene promoter -607, -656 position (rs1946519, rs1946518), IL10 gene promoter -592, -819, -1082 position (rs1800872, rs1800871, rs1800896) and the information received was attributed to the phenotypic manifestations of the disease. The study obtained reliable results about the association of the genetic markers with RA susceptibility, activity and severity. Summarizing data about genetic markers, it is evident that one polymorphism affects development of various symptoms of the disease. At the same time different genetic factors participate in the formation of the particular phenotype. PTPN22 1858C/T, KLF12C/A, IL6 and IL18 polymorphisms are associated with susceptibility to RA in Latvian population. KLF12C/A and IL6 polymorphisms may affect antibodies status. PTPN22 1858T allele bearing genotypes and KLF12 A allele homozygous genotype are possibly the forerunners of erosive disease. TNFA genotypes may influence disease pathogenesis, depending on the age of disease onset and IL10 promoter polymorphisms may influence disease activity. This study combines several scientific fields – genetics, biology, medicine. The results obtained are comparable with similar international studies. Knowledge about the association between genetic factors and disease supplement existing information about etiology and pathogenesis of RA, factors that affect disease activity, severity and prognosis, help in early diagnosis of RA, in prediction of disease manifestations and treatment planning with potential clinical and economic benefits.