A Haplotype at the COL9A2 Gene Locus Contributes to the Genetic Risk for Lumbar Spinal Stenosis in the Korean Population

We conducted a cross-sectional, genotyping study in patients with lumbar spinal stenosis (LSS) and controls. To determine the contribution of COL9A2 polymorphisms to LSS development in the Korean population. Because congenital spinal stenosis is typically associated with chondrodysplasias, which are genetic disorders, genetic factors may also play a role in degenerative LSS. A recent Finnish study reported a splice site mutation in COL9A2, leading to premature translation termination. However, a few studies on the genetic association of single nucleotide polymorphisms (SNPs) or haplotypes with LSS have appeared. We studied 205 symptomatic patients with radiographically proven LSS and 101 volunteers with no history of back problems from our institution. Magnetic resonance images were obtained for all the patients and controls. Quantitative image evaluation for LSS was performed to evaluate the severity of LSS. All patients and controls were genotyped for COL9A2 allele variations, using a polymerase chain reaction-based technique. We found no causal SNPs in COL9A2 that were significantly associated with LSS, even after phenotypic subgrouping. Haplotype analysis showed that the "GCAGCG" haplotype (HAP2) was overrepresented in LSS patients (P = 0.023, odds ratio [OR] = 1.86), especially in those with severe stenosis (P = 0.018, OR = 1.98). In addition, the "TCAGCG" haplotype (HAP4) was overrepresented in controls (P = 0.042, OR = 0.52). Although no SNPs in COL9A2 were associated with LSS, a COL9A2 haplotype (HAP2) was significantly associated with LSS in the Korean population, whereas another haplotype (HAP4) may play a protective role against LSS development. However, the genetic functions of COL9A2 haplotypes in LSS remain to be determined.