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

Abstract

Chemokine C-C motif ligand 4 (CCL4) gene is a chemokine-encoding gene, and the polymorphism of CCL4 gene has been shown to predict risk of various diseases. We want to investigate whether the single nucleotide polymorphisms (SNPs) of the CCL4 gene can predict the risk of rheumatoid arthritis (RA). Between 2007 and 2015, we recruited 217 patients diagnosed with RA and 371 control participants. Comparative genotyping of the rs1634507, rs10491121, and rs1719153 SNPs was performed. When compared with participants with the A/A genotype of rs1719153, those with the A/T genotype were less likely to develop RA, as were those with the A/T+T/T genotype. The protective effect of the T-containing genotype was even more prominent among females. Those with A/T in rs1719153 were 56% less likely to develop RA compared with females with A/A; a similar protective effect was seen for females with the A/T+T/T genotype compared with those with A/A. The GTEx database revealed that patients carrying the T/T genotype had lower levels of CCL4 gene expression than those carrying the A/A genotype. These results indicate that the nucleotide T over the rs1719153 is associated with decreased CCL4 gene expression and decreased risk for RA.

Correlation between genetic polymorphism of angiopoietin-2 gene and clinical aspects of rheumatoid arthritis

“…The RA susceptibility is influenced by genetic factors. Although the advent of biological-based antirheumatic therapies has enabled some patients to achieve very low levels of disease activity, there are still an unignorable number of RA patients who remain treatment-refractory 1, 25, 26. The unmet need underlines the importance of continuing to investigate the pathogenesis of RA.…”

“…Rheumatoid arthritis (RA) is manifested by marked hypertrophy, hypervascularity of the synovial tissues and consequent joint destruction, plaguing around 1% of the global population 1, 2. Despite the recent advent of biological agents enabling some RA patients to achieve disease remission with minimal symptoms, a marked proportion of patients remain treatment-refractory and suffer from progressive joint destruction, functional deterioration or even premature mortality 3-5.…”

“…Single nucleotide polymorphisms (SNPs) denote the single nucleotide variations occurring at specific sites in the genome with substantial frequency within the population 1, 9, 10. Genotyping SNPs and comparing the frequency of SNPs among subgroups (e.g., controls and patients) are frequently utilized to examine the risk and prognosis of human, including RA 6, 10, 11.…”

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].…”

“…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]. The fact that genetic factors account for around 60% of the overall susceptibility to RA highlights the importance of research into the genetic basis for RA [5,9]. Research into RA genetics may facilitate risk prediction and enable individually…”