CHRNA5/CHRNA3 gene cluster is a risk factor for lumbar disc herniation: a case-control study

Abstract

Background: Lumbar disc herniation, a type of chronic low back pain syndrome, is caused by the lumbar intervertebral disk degeneration. Genetic variation in the CHRNA5/CHRNA3 has shown strong associations with smoking-related diseases. This study's aim is to test whether single-nucleotide polymorphisms in the CHRNA5/CHRNA3 gene are associated with lumbar disc herniation risk.

Methods: The genotype frequency distributions of the polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism in 380 lumbar disc herniation patients (case group) and 400 healthy individuals (control group). Allelic, genotypic, and haplotype analyses were performed.

Results: We found that the individuals with rs8040868 CT genotype had a 0.46-fold higher risk of lumbar disc herniation than those with rs8040868 TT genotype, in men group (OR = 0.46, 95% CI 0.25-0.84, p = 0.012). Also among women, rs8040868 CT + CC genotype still reduced the risk of lumbar disc herniation under the dominant model (OR = 0.50, 95% CI 0.28-0.89, p = 0.019). Haplotype analysis showed that compared with the CHRNA5 "TACAACCG" wild-type, the "TACACCCG" haplotype was found to be associated with a decreased risk of lumbar disc herniation (LDH) (OR = 0.79, 95% CI 0.63-1.00, p = 0.047), while, in the less than 50-year-old group, CHRNA5 "TACACCCG" increased the risk of LDH (OR = 1.46, 95% CI 1.01-2.13, p = 0.047).

Conclusions: Our data suggest that gene variance in the CHRNA5/CHRNA3 is associated with risk of lumbar disc herniation in the case-control study.

Keywords: CHRNA5/CHRNA3; Lumbar disc herniation; Single-nucleotide polymorphism; Susceptibility.

Fig. 1

LD structures of the 15 SNPs genotyped in CHRNA5/CHRNA3 gene. The LD strengths between paired SNPs are shown in color according to the confidence intervals’ model. Red squares display statistically significant associations between a pair of SNPs, as measured by D’; darker shades of red indicate higher D’