Pathway-based association analysis of two genome-wide screening data identifies rheumatoid arthritis-related pathways.

The pathways can explain molecular mechanisms of complex diseases from the perspective of biology function. We carried out a genome-wide pathway-based association analysis to identify the risk pathways of rheumatoid arthritis (RA). First, we performed two genome-wide association studies using two RA data sets from GAW16 (Genetic Analysis Workshop 16) and the Wellcome Trust Case Control Consortium, and obtained risk P-value for each single-nucleotide polymorphism (SNP). Next, we mapped all the SNPs to genome-wide autosomal genes and calculated gene-wise risk values by minimum P-value method. We calculated the KEGG (Kyoto Encyclopedia of Gene and Genomes) pathway risk scores according to Fisher combination method and identified the significant pathways by permutation test. At last, we merged the results from the two pathway-based genome-wide association analyses to identify the high-risk pathways, which were found in both the data sets. The results showed that there were nine pathways, focal adhesion pathway, extracellular matrix-receptor interaction pathway, calcium signaling pathway, dopaminergic synapse pathway, long-term potentiation pathway, retrograde endocannabinoid signaling pathway, glutamatergic synapse pathway, cholinergic synapse pathway and morphine addiction pathway, associated with susceptibility to RA. Among these pathways, four pathways were reported as RA-risk pathways in the previous literatures. We also inferred that other five pathways may be related to RA. Further researches of these pathways will help us to understand the molecular mechanisms of RA.

Role of Hsa-miR-122-3p in steroid-induced necrosis of femoral head.

OBJECTIVE: To explore the clinical correlation between the hsa-miR-122-3p expression in bone marrow mesenchymal stem cells (BMSCs) and steroid-induced necrosis of femoral head (SONFH). PATIENTS AND METHODS: A total of 62 SONFH patients were selected as the experimental group, while another 72 patients with femoral neck fracture (FNF) were selected as the control group. The bone marrow was obtained from patients during operation and used to culture the BMSCs. The expression of hsa-miR-122-3p in BMSCs was detected via real-time quantitative polymerase chain reaction (qPCR) in both groups. The patients in experimental group were further divided into Ficat stage III group and stage IV group according to the Ficat stage, and the expression of hsa-miR-122-3p in BMSCs was also detected via qPCR in the two groups. RESULTS: The expression level of hsa-miR-122-3p in SONFH group was significantly lower than that in FNF group, and the difference was statistically significant (p<0.05). The expression level of hsa-miR-122-3p in Ficat stage IV group was significantly lower than that in stage III group (p<0.05). CONCLUSIONS: We demonstrated that the expression of hsa-miR-122-3p in BMSCs declined in SONFH group, indicating that hsa-miR-122-3p may be involved in the regulation of the pathological process of SONFH, and the expression level of hsa-miR-122-3p in BMSCs may be correlated with the progression of SONFH.