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

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Shu-Jui Kuo ◽  
Chien-Chung Huang ◽  
Chun-Hao Tsai ◽  
Horng-Chaung Hsu ◽  
Chen-Ming Su ◽  
...  

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.

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Erika Calvano Küchler ◽  
Agnes Schröder ◽  
Vinicius Broska Teodoro ◽  
Ute Nazet ◽  
Rafaela Scariot ◽  
...  

Abstract Background This study aimed to investigate, if different physiological concentrations of vitamin D (25(OH)D3) and single nucleotide polymorphisms in vitamin D receptor (VDR) gene have an impact on gene expression in human periodontal ligament (hPDL) fibroblasts induced by simulated orthodontic compressive strain. Methods A pool of hPDL fibroblasts was treated in absence or presence of 25(OH)D3 in 3 different concentrations (10, 40 and 60 ng/ml). In order to evaluate the role of single nucleotide polymorphisms in the VDR gene, hPDL fibroblasts from 9 patients were used and treated in absence or presence of 40 ng/ml 25(OH)D3. Each experiment was performed with and without simulated orthodontic compressive strain. Real-time PCR was used for gene expression and allelic discrimination analysis. Relative expression of dehydrocholesterol reductase (DHCR7), Sec23 homolog A, amidohydrolase domain containing 1 (AMDHD1), vitamin D 25-hydroxylase (CYP2R1), Hydroxyvitamin D-1-α hydroxylase, receptor activator of nuclear factor-κB ligand (RANKL), osteoprotegerin (OPG), cyclooxygenase-2 (COX-2) and interleukin-6 (IL6) was assessed. Three single nucleotide polymorphisms in VDR were genotyped. Parametric or non-parametric tests were used with an alpha of 5%. Results RANKL, RANKL:OPG ratio, COX-2, IL-6, DHCR7, CYP2R1 and AMDHD1 were differentially expressed during simulated orthodontic compressive strain (p < 0.05). The RANKL:OPG ratio was downregulated by all concentrations (10 ng/ml, 40 ng/ml and 60 ng/ml) of 25(OH)D3 (mean = 0.96 ± 0.68, mean = 1.61 ± 0.66 and mean = 1.86 ± 0.78, respectively) in comparison to the control (mean 2.58 ± 1.16) (p < 0.05). CYP2R1 gene expression was statistically modulated by the different 25(OH)D3 concentrations applied (p = 0.008). Samples from individuals carrying the GG genotype in rs739837 presented lower VDR mRNA expression and samples from individuals carrying the CC genotype in rs7975232 presented higher VDR mRNA expression (p < 0.05). Conclusions Simulated orthodontic compressive strain and physiological concentrations of 25(OH)D3 seem to regulate the expression of orthodontic tooth movement and vitamin-D-related genes in periodontal ligament fibroblasts in the context of orthodontic compressive strain. Our study also suggests that single nucleotide polymorphisms in the VDR gene regulate VDR expression in periodontal ligament fibroblasts in the context of orthodontic compressive strain.


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