A novel variant near LSP1P3 is associated with knee osteoarthritis in the Chinese population.

Abstract

Previous genome-wide association study showing a novel variant near LSP1P3 was associated with knee osteoarthritis (KOA) in Caucasians. Replication study in different populations was essential to validate the association of novel susceptible genes with KOA. To our knowledge, there is a lack of study concerning the role of the LSP1P3 gene in Chinese KOA patients. We aimed to determine the association between the novel variant near LSP1P3 gene and the susceptibility of KOA in the Chinese population and to further investigate its relationship with the severity of KOA. A total of 532 primary KOA patients who received treatment in our clinic center were included in the current study. Nine hundred twenty-seven age- and gender-matched healthy subjects were recruited as controls. The severity of KOA was graded according to the Kellgren-Lawrence (KL) grading system, with KL grade of 1 or 2 classified as mild KOA and KL grade of 3 or 4 classified as severe KOA. Three variants were genotyped using TaqMan SNP genotyping assay, including rs4867568 of LSP1P3 gene, rs143383 of GDF5, and rs1558902 of FTO. The differences in terms of genotype and allele distributions between the cases and the controls were analyzed by the chi-square test. There were 215 male and 317 female patients with a mean age of 58.1 ± 7.2years. According to the KL score, 172 (32.3%) patients had mild KOA and 360 (67.7%) had severe KOA. There were remarkably lower frequencies of allele T of rs4867568 and allele C of rs143383 in the patients than in the controls (31.5% vs. 36.0%, p = 0.01 for rs4867568; 24.6% vs. 28.7%, p = 0.02 for rs143383), with an OR of 0.82 and 0.81, respectively. As for rs1558902, no significant difference regarding the frequency of allele and genotype was found between the patients and the controls. Patients with severe KOA had remarkably lower incidence of genotype TT of rs4867568 than patients with mild KOA (6.7% vs. 12.2%, p = 0.04). There was significantly higher frequency of allele T in patients with mild KOA than in those with severe KOA (36.3% vs. 29.2%, p = 0.02, OR = 0.72). The association of rs4867568 and rs143383 with KOA was successfully replicated in the Chinese Han population. Moreover, rs4867568 was found significantly associated with the severity of KOA. More studies are warranted to explore the functional role of rs4867568 in the development of KOA. Key Points • A novel variant near Lsp1p3 is associated with knee osteoarthritis. • Baseline characteristics of the subjects. • Comparison of the genotype and allele frequency of the Lsp1p3, GDF5, and FTO. • Association of the Lsp1p3, GDF5, and FTO with KOA severity.