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

Zhengming Sun¹, Ming Ling, Yanhai Chang

¹Department of Orthopaedics, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, China. szmnx3@yahoo.cn

Connective Tissue Research

|December 5, 2012

Abstract

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 Data:

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.

Conclusion:

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

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