Prognostic significance of high-mobility group box protein 1 genetic polymorphisms in rheumatoid arthritis disease outcome

Abstract

Rheumatoid arthritis (RA) is a systemic inflammatory disease that causes chronic inflammation of the joints. Analysis of genetic variants offers promise for guiding treatment and improving outcomes in RA. High-mobility group box protein 1 (HMGB1) is a ubiquitous nuclear protein found in all mammal eukaryotic cells that participates in several biological functions including immune response, cell survival and apoptosis. We investigated the effects of HMGB1 gene polymorphisms on the risk of RA disease progression in a cohort of Chinese Han individuals. Four single nucleotide polymorphisms (SNPs) from the HMGB1 gene were selected and genotyped in 232 patients with RA and 353 healthy controls. We found that having one C allele in rs1360485 and one G allele in rs2249825 polymorphisms lowered the risk of RA in females. Moreover, among healthy controls, those who bore the C/G/T haplotype at SNPs rs1360485, rs2249825 and rs1412125 were at reduced risk of developing RA by 0.13-fold (p <0.05). This is the first report to examine the risk factors associated with HMGB1 SNPs in the development of RA disease in the Chinese Han population.

Chemokine C-C Motif Ligand 4 Gene Polymorphisms Associated with Susceptibility to Rheumatoid Arthritis

“…It is well recognized that susceptibility for RA disease is influenced by genetic and environmental factors [ 22 , 23 ]. The recent development of biological-based antirheumatic therapies that target inflammatory pathways in RA has enabled increasing numbers of patients to achieve very low levels of disease activity, yet a substantial proportion of RA patients remain treatment-refractory [ 3 , 24 ]. This issue underlines the importance of continuing to investigate the pathogenesis of RA.…”

“…Rheumatoid arthritis (RA) is an autoimmune disease characterized by marked hypertrophy and hypervascularity of the synovial tissues and joint destruction, affecting around 1% of the global population [ 1 , 2 ]. Despite the emergence of promising novel therapies in recent years that have enabled a substantial amount of RA patients to achieve disease remission with minimal or no symptoms, a substantial proportion of patients remain treatment-refractory and experience progressive joint and functional destruction or even premature mortality [ 3 , 4 ]. The mortality rates among the RA patients are 1.5 ~ 1.6 times higher than those among the general population [ 5 , 6 ].…”

“…The risks of major morbidities, including infection and pulmonary and renal disease, are also higher among the RA patients than among the general population [ 5 ]. The recognition that genetic factors account for up to 60% of the overall susceptibility and development of RA highlights the importance of research into genetic aberrations of this disease [ 3 , 7 , 8 ]. Investigations into RA genetics may help to facilitate risk prediction for individual patients and tailor their treatment accordingly [ 3 ].…”

VEGF-C Gene Polymorphisms Increase Susceptibility to Rheumatoid Arthritis

“…Rheumatoid arthritis (RA) is an autoimmune disease that manifests hypertrophy and hypervascularity in synovial tissues and leads to joint destruction, affecting approximately 1% of the global population [1][2][3][4]. Despite several treatment regimens emerging in recent years that have enabled a substantial portion of RA patients to achieve disease remission with minimal symptoms, some patients remain treatment-refractory and continue to experience progressive joint deterioration and increasing functional limitations, or even premature mortality [5][6][7]. When compared with the general population, RA patients face higher risks of major morbidities, including infection and pulmonary and renal disease, and an approximate 1.5-fold higher risk of mortality [8].…”

HMGB1 genetic polymorphisms are biomarkers for the development and progression of breast cancer

“…HMGB1 is usually localized in the cell nucleus and is secreted into the extracellular environment in response to different stimuli; either passively during cellular apoptosis or necrosis, or actively following inflammatory signals from activated immune cells or neuronal cells 9 . It has been reported HMGB1 SNPs controls with rheumatoid arthritis disease outcome 10 . Previous research has confirmed the association of HMGB1 SNPs with the susceptibility and progression of disease, such as hepatocellular carcinoma 11 , lung cancer 12 and uterine cervical neoplasia 13 .…”