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

Xuejun Yang,Yong Zhu,Feng Li,Ke Sun,Manglai Li,Haiyu Jia,Xiaodong Guo,Wenhua Xing,Yifeng Da,Zhi Huang

doi:10.1186/s13018-019-1254-2

Abstract

BackgroundLumbar 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.MethodsThe 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.ResultsWe 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).ConclusionsOur data suggest that gene variance in the CHRNA5/CHRNA3 is associated with risk of lumbar disc herniation in the case-control study.

Highlights

Lumbar disc herniation (LDH) is one of the more common spinal diseases caused by the degeneration and the displacement of nucleus pulposus or annulus fibrosis beyond the intervertebral disc space [1]
The results of the Hardy–Weinberg equilibrium (HWE) showed that the genotype frequency distributions of CHRNA5/CHRNA3 in the case and control groups were in line with genetic balance, which showed that all of the 15 tag Single-nucleotide polymorphisms (SNPs) were at equilibrium and were representative
LDH lumbar disc herniation, SNP single-nucleotide polymorphism, MAF minor allele frequency, HWE Hardy–Weinberg equilibrium, Odds ratios (ORs) odds ratio, 95% confidence intervals (CIs) 95% confidence interval † p was calculated by exact test ‡ p was calculated by Pearson chi-squared test

Summary

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).

Results

Introduction

Material and methods

Discussion

Conclusion