Single-nucleotide gene polymorphisms involving cell death pathways: a study of Chinese patients with lumbar disc herniation.

OBJECTIVE

To evaluate the effect of polymorphisms of death pathway genes FAS and FASL on the risk of developing lumbar disc herniation (LDH) in a Northern Chinese population.

BACKGROUND

The FAS receptor-ligand system plays a key role to regulate apoptosis of cell. There is evidence that the apoptosis-mediated FAS receptor-ligand system is involved in the pathogenesis of disc degeneration. Some research considered single-nucleotide polymorphisms of FAS-1377G/A, FAS-670A/G, FASL-844T/C, and FASL INV2nt-124A/G may increase the risk of developing cancer. We therefore assess these four single-nucleotide polymorphisms as candidate susceptibility for LDH.

METHODS

A total of 475 patients with LDH and 533 control subjects were selected. Genotypes were determined by polymerase chain reaction-based restriction fragment length polymorphism and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Associations with the risk of LDH were estimated by logistic regression model.

RESULTS

Significant differences were found in genotypic distributions between cases and controls for FASL-844T/C, but not for other three polymorphisms. When compared with CC genotype, subjects with the TT genotype had a higher risk to develop LDH (odds ratio = 3.12; 95% confidence interval: 1.73-5.40). Moreover, an association was found between this genotype of FASL-844TT and more severe grades of disc degeneration. We observed statistically significant interactions between polymorphisms of FASL-844T/C and lumbar load, tobacco smoking, and age.

CONCLUSIONS

Genetic polymorphisms of FASL-844T/C may be associated with an increased risk of developing disc degeneration and LDH.