Putative functional variants of PI3K/AKT/mTOR pathway are associated with knee osteoarthritis susceptibility

Background Osteoarthritis (OA) is a degenerative musculoskeletal disease which causes joint deformity and pain and finally leads to limb dysfunction. Knee osteoarthritis (KOA) has the highest incidence among all kinds of OA. Strong evidence leads to the understanding that P13K/AKT/mTOR signaling is very important in cartilage degeneration. Methods This research sought to understand the association between genetic variation of PI3K/AKT/mTOR genes and KOA susceptibility among Chinese population. All the genetic variants of PI3K/AKT/mTOR pathway were graded and selected using RegulomeDB database, and then, an association study including 278 osteoarthritis patients and 289 controls was conducted. Results Finally, eight SNPs' genotypes' distributions and susceptibility to KOA were presented. AKT1 rs2498789 was associated with KOA susceptibility in dominate genetic model (AA + GA vs GG) after adjusted for BMI, age, and gender: OR = 1.46, 95% CI: 1.03-2.05, P = .03. PIK3CA rs7646409 was also associated with KOA susceptibility (TC vs TT) after adjusted for BMI, age, and gender: OR = 0.58, 95% CI: 0.36-0.93, P = .02. PIK3CA rs7646409 (TC vs TT) with KOA risk was more significant in age < 60 group (P for heterogeneity was .03). Risk score showed significant association with KOA susceptibility after cumulative analysis (OR = 2.45, 95% CI: 1.35-4.45, P = .003). Conclusions This study shows that genetic variation of PI3K/AKT/mTOR is associated with KOA susceptibility in Chinese Han population, indicating that PI3K/AKT/mTOR is very important in KOA pathogenesis.