نبذة مختصرة : 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.
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