Common variants in the GNL3 contribute to the increasing risk of knee osteoarthritis in Han Chinese population

Bo Liu,Xiaoqian Dang,Wenlong Ma,Xiangyang Wang,Huiguang Cheng,Futai Gong,Ning Duan

doi:10.1038/s41598-018-27971-4

Abstract

Osteoarthritis (OA) is a complex degenerative joint disorder, which is caused by both environmental and genetic factors. Previous studies have indicated that the GNL3 gene is associated with knee osteoarthritis (KOA) susceptibility in Europeans; however, the exact molecular mechanism is still unclear. In the present study, we investigated the potential genetic association of GNL3 with KOA in a two-stage sample of 6,704 individuals from the Han Chinese population. Subjects containing 1,052 KOA patients and 2,117 controls were considered the discovery dataset, while subjects consisting of 1,173 KOA patients and 2,362 controls were utilized as the replication dataset. Single-SNP association, imputation, and haplotypic association analyses were performed. The SNP of rs11177 in GNL3 was identified to be significantly associated with KOA after accounting for age, gender and BMI in both stages. The imputed SNP of rs6617 in SPCS1 was found to be strongly associated with KOA risk, and the significant association signal was confirmed in the replication stage. Moreover, a haplotype-based analysis also indicated a positive genetic effect of GNL3 on KOA susceptibility. In summary, our results proved that GNL3 plays an important role in the etiology of KOA, suggesting that GNL3 is a potential genetic modifier for KOA development.

Highlights

Osteoarthritis (OA) is the most common form of arthritis worldwide and is caused by degenerative changes in articular cartilage[1]
We investigated the potential genetic association between GNL3 and knee osteoarthritis (KOA) to determine whether or not GNL3 is associated with KOA in a Han Chinese population
Previous studies have indicated that many common variants are involved in KOA susceptibility, but the exact mechanism of these genetic variants resulting in a risk of KOA remains unclear

Summary

Introduction

Osteoarthritis (OA) is the most common form of arthritis worldwide and is caused by degenerative changes in articular cartilage[1]. Many of the risk genes contributing to KOA susceptibility have been reported in previous studies. Among these candidate genes, the GNL3 gene has gained much attention. A previous study demonstrated that certain genes, including SPCS1, which surrounds GNL3, and GNL3, had an allelic expression imbalance in the same direction, with the minor allele producing fewer transcripts than the major allele[20]. These results further prove that GNL3 may involve in the pathogenesis of OA. We investigated the potential genetic association between GNL3 and KOA to determine whether or not GNL3 is associated with KOA in a Han Chinese population

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Conclusion