Objectives
A recently published genome-wide association study identified six novel loci associated with rheumatoid arthritis (RA) in Korean population. We aimed to investigate whether these newly reported RA-risk loci are associated with RA in the Chinese population and to further characterize the functional role of the susceptible gene.
Methods
The susceptible variants of RA were genotyped in 600 RA patients and 800 healthy controls, including rs148363003 of SLAMF6, rs117605225 of CXCL13, rs360136 of SWAP70, rs111597524 of NFKBIA, rs194757 of ZFP36L1 and rs1547233 of LINC00158. Synovial tissues were collected from the knee joint of 50 RA patients and 40 controls without osteoarthritis for the gene expression analysis. Inter-group comparisons were performed with the Chi-square test for genotyping data or with Student's t-test for gene expression analysis.
Result
For rs148363003 of SLAMF6, RA patients were observed to have a significantly lower frequency of genotype CC (4.5% vs. 0.9%, p = 0.004) as compared with the controls. The frequency of allele C was remarkably higher in the patients than in the controls (11.5% vs. 8.0%, p = 0.002), with an odds ratio of 1.49 (95% CI = 1.16–1.92). There was no significant difference between the patients and the controls regarding genotype or allele frequency of the other 5 variants. The mRNA expression of SLAMF6 was 1.6 folds higher in the RA patients than in the controls. Moreover, SLAMF6 expression was 1.5 folds higher in patients with genotype CC than in the patients with genotype TT.
Conclusions
SLAMF6 was associated with both the susceptibility and severity of RA in the Chinese population. Moreover, rs148363003 could be a functional variant regulating the tissue expression of SLAMF6 in RA patients. It is advisable to conduct further functional analysis for a comprehensive knowledge on the contribution of this variant to the development of RA.
The abnormal expression of miRNA-146a is related to the progression of coronary arteries. This study intends to explore the protective effect of miRNA-146a on vascular smooth muscle cells (VSMCs) after coronary intervention and the related mechanism. 10 miniature pigs were randomly
assigned into control group, model group, blank group, miRNA-146a group, cilostazol group, and STAT3 signaling agonist group followed by analysis of the morphology and viability of VSMCs, expression of miRNA-146a, STAT3, NF-kB, TNF-a, IL-6, and AT-1R as well as the relationship between miR-146a
and STAT3. The BNP (192.39±12.32) pg/ml and cTnI (14.20±2.12) μg/L of model group were significantly higher than those of control group (P < 0.05). miRNA-146a level was highest in miRNA-146a group and cilostazol group, while lower in other two groups with
the lowest level in agonist group (P <0.05). The cell viability and AngII level of miRNA-146a group and cilostazol group were lower, and higher in the other two groups with highest level in pathway agonist group (P < 0.05). miRNA-146a group and cilostazol group showed lower
expressions of STAT3, NF-kB, TNF-a, IL-6, AT-1R than the other two groups. The pathway agonist group showed significantly higher level than blank group (P <0.05). liposome nanoparticles carrying miRNA-146a inhibited the activity of STAT3 signaling, down-regulated the levels of downstream
factors including TNF-a, IL-6, and TNF-a and subsequently decreased AngII and AT-1R levels, therefore playing a protective effect on VSMCs after coronary intervention.
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