Assessment of NMDA receptor genes (GRIN2A, GRIN2B and GRIN2C) as candidate genes in the development of degenerative lumbar scoliosis

Degenerative lumbar scoliosis (DLS) progresses with aging after 50-60 years. The genetic association of DLS remains largely unclear. In this study, the genetic association between glutamate receptor, ionotropic, N-methyl D-aspartate (NMDA, GRIN) receptor genes and DLS was investigated. A total of 9 coding single nucleotide polymorphisms (cSNPs) in NMDA receptor genes [GRIN2A (rs8049651, Leu425Leu; rs9806806, Tyr730Tyr); GRIN2B (rs7301328, Pro122Pro; rs35025065, Asp447Asp; rs1805522, Ile602Ile; rs1806201, Thr888Thr; rs1805247, His1399His); and GRIN2C (rs689730, Ala33Ala; rs3744215, Arg1209Ser)] were selected and genotyped using direct sequencing in 70 patients with DLS and 141 healthy controls. Multiple logistic models (codominant, dominant and recessive) were calculated for the odds ratio (OR), 95% confidence interval (CI) and corresponding P-values. The SNPStats, SNPAnalyzer and HelixTree programs were used for the evaluation of the genetic data. Among the SNPs examined, no significant associations were observed between the NMDA receptor genes and DLS. When the patients were divided into two groups according to clinical characteristics based on Cobb's angle (<20° or ≥20°) and lateral listhesis (<6 mm or ≥6 mm), associations were observed between rs689730 of GRIN2C and Cobb's angle (codominant, P=0.038; dominant, P=0.022) and between rs7301328 of GRIN2B and lateral listhesis (codominant, P=0.003; dominant, P=0.015; recessive, P=0.015). These results indicate that the GRIN2A, GRIN2B and GRIN2C genes do not affect the development of DLS. However, the GRIN2C gene may be associated with Cobb's angle, while the GRIN2B gene may be associated with lateral listhesis.