Common variants in GNL3 gene contributed the susceptibility of hand osteoarthritis in Han Chinese population

Abstract

Osteoarthritis (OA) is one of the most popular degenerative joint diseases. The nucleolar GTP binding protein 3 (GNL3) gene encodes guanine nucleotide binding protein-like 3, which is related in cell proliferation, differentiation, and cell cycle regulation. Our study aimed to examine the contribution of GNL3 gene polymorphisms to the risk of hand OA and its related clinical features. A total of 3387 study participants including 1160 patients with hand OA and 2227 controls were recruited in this study. Eleven SNPs in GNL3 gene were selected for genotyping. Genetic association signals were examined using Plink. Relationships between significant SNPs and clinical features of hand OA were also explored. SNP rs11177 was found to be strongly associated with susceptibility of hand OA (P = 4.32 × 10–5). The minor allele of rs11177 was associated with increased susceptibility of hand OA. In addition, significant associations were also identified between genotypes of rs11177 and clinical features of hand OA patients including K-L grade (P < 0.01) and categorized pain scores (P < 0.01). Significant eQTL signals for rs11177 on GNL3 in multiple types of human tissues were also identified in GTEx database. Our results have established the link between GNL3 gene and susceptibility of hand OA.

Intergenic Interactions of SBNO1, NFAT5 and GLT8D1 Determine the Susceptibility to Knee Osteoarthritis among Europeans of Russia

“…In Gee et al, the correlations of two polymorphic loci of the genes SPCS1 (rs6617) and GNL3 (rs11177), which are strongly coupled with rs6976 GLT8D1 , with a significant imbalance of gene expression ( SPCS1 and GNL3 , respectively) in cartilage and other joint tissues such as ligaments, meniscus, adipose tissue, synovial membrane, were shown [ 97 ]. A number of studies have established the association of the rs11177 (G>A) GNL3 with the OA risk in both European and Asian populations [ 1 , 31 , 32 , 99 ], including on the GWAS level ( p ≤ 5 × 10 −8 ) [ 31 , 32 ].…”

“…Osteoarthritis (OA) is a common chronic degenerative joint disease [ 1 ], resulting in pathological changes in all joint tissues (cartilage/subchondral bone/ligaments/menisci/articular capsule/synovial membrane) [ 2 ]. More than 500 million people worldwide suffer from this disease; an especially high incidence of OA is observed among people over 65 years of age [ 3 ].…”

Emerging roles ofRNAbinding proteins in intervertebral disc degeneration and osteoarthritis

“…It has been implicated in multiple bioprocesses, including cell proliferation, differentiation, and cell cycle regulation. [116][117][118] GNL3 belongs to the GTP-binding protein family, containing an MMRHSR1 domain. 119 GNL3 is abundantly expressed in bone marrow mesenchymal stem cells (BM-MSCs) and is closely related to the differentiation of chondrocytes.…”

“…119 GNL3 is abundantly expressed in bone marrow mesenchymal stem cells (BM-MSCs) and is closely related to the differentiation of chondrocytes. [116][117][118] Recently, both human and animal studies found that GNL3 were significantly reduced in knee tissues of OA samples compared with non-OA samples. However, the potential mechanism underlying aberrant GNL3 expression in OA remains unclear.…”

“…GTP‐binding protein 3 (GNL3), known as nucleostemin, also plays an important role in PTGR involved in different stages of RNA metabolism. It has been implicated in multiple bioprocesses, including cell proliferation, differentiation, and cell cycle regulation 116–118 . GNL3 belongs to the GTP‐binding protein family, containing an MMRHSR1 domain 119 .…”