A controlled case study of the relationship between environmental risk factors and apoptotic gene polymorphism and lumbar disc herniation

Am J Pathol. 2013 Jan;182(1):56-63. doi: 10.1016/j.ajpath.2012.09.013. Epub 2012 Nov 7.


To explore the etiologic role of apoptosis-related genes, environmental risk factors, and their interaction in the occurrence of lumbar disk herniation (LDH), a controlled case study was performed with 128 LDH patients and 132 age- and sex-matched controls. Matrix-assisted laser desorption/ionization, time-of-flight mass spectrometry assay was used to analyze the genotype of nine polymorphism sites in three genes, including Fas -1377G/A rs2234767, Fas -670G/A rs1800682, Fas rs2147420, Fas rs2296603, Fas rs7901656, Fas rs1571019, Fas ligand (FasL) -844C/T rs763110, caspase 9 (CASP9) -1263A>G rs4645978, and CASP9 -712C>T rs4645981. The patients and controls showed similar age and sex, but had significant differences in lumbar load, bed type, amateur sports, and leisure activities (P < 0.05). The correlation analysis revealed that polymorphism of FasL -844C/T (rs763110) and CASP9 -1263A>G (rs4645978) had a significant correlation with LDH, indicating that the genotypes of FasL -844C/T TT and CASP9 -1263A>G GG are probably high-risk genotypes for LDH. The results of environment-gene interaction analysis revealed that, in LDH, the interaction of the FasL -844TT genotype and level III to IV lumbar load was consistent with the ultramultiplying model, and the interaction of the CASP9 rs4645978 GG genotype and level III to IV lumbar load was consistent with the submultiplicative model. Therefore, the risk of LDH was determined by both environmental and genetic risk factors, and the mechanisms of interactions between different genotypes and environmental factors also differed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Apoptosis / genetics*
  • Case-Control Studies
  • Female
  • Gene-Environment Interaction*
  • Genetic Predisposition to Disease
  • Humans
  • Intervertebral Disc Displacement / etiology*
  • Intervertebral Disc Displacement / genetics
  • Intervertebral Disc Displacement / pathology
  • Intervertebral Disc Displacement / physiopathology
  • Lumbar Vertebrae* / physiopathology
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Risk Factors
  • Weight-Bearing