Association between BMP-2 and COL6A1 gene polymorphisms with susceptibility to ossification of the posterior longitudinal ligament of the cervical spine in Korean patients and family members

Abstract

ABSTRACT. COL6A1 and BMP-2 genes have been implicated in ossification of the posterior longitudinal ligament (OPLL) susceptibility in Japanese and Chinese Han populations. However, no study has yet investigated the DNA of unaffected family members of patients with OPLL. This study investigated differences in genetic polymorphisms of BMP-2 and COL6A1 between Korean patients with OPLL and their family members (with and without OPLL). A total of 321 subjects (110 patients with OPLL and 211 family members) were enrolled in the study. Associations between two single nucleotide polymorphisms (SNPs) of the BMP-2 gene (Ser37Ala and Ser87Ser) and two SNPs of COL6A1 [promoter (-572) and intron 33 (+20)] with susceptibility to OPLL of the cervical spine were investigated between the two groups (OPLL+ BMP-2 and COL6A1 polymorphisms and OPLL in Koreans and OPLL-). Of the 321 subjects, 162 had cervical OPLL (50.4%; 110 patients, 52 family members). There was a familial tendency of OPLL in 34 of the 110 families (30.9%). Allele and haplotype frequencies of the four SNPs in the BMP-2 and COL6A1 genes did not differ significantly between the OPLL+ and OPLL-groups, even when excluding participants over 50 years of age. This is the first report identifying SNPs of COL6A1 and BMP-2 in Korean patients and family members with OPLL. Although allele and haplotype frequencies were similar with those of a previous study in Japanese and Chinese patients, unaffected family members also showed similar rates of these SNPs in the present study. These results suggest that these SNPs may not directly influence the expression of OPLL.

Identification of susceptibility loci for thoracic ossification of the posterior longitudinal ligament by whole-genome sequencing

“…Chronic compression of the spinal cord and nerve root leads to spinal cord compression symptoms and radiculopathy in patients with OPLL. The severity of the symptoms is associated with the size and segmentation of the ossifying ligament, and 70% of OPLL occurs in the cervical spine, whereas 15% occurs in the thoracic spine (1). Notably, as early as 1972, researchers reported that thoracic OPLL (T-OPLL) can cause thoracic spinal stenosis (2).…”

Genetics of Degenerative Cervical Myelopathy: A Systematic Review and Meta-Analysis of Candidate Gene Studies

“…However, Liu et al (2010) reported no significant effect of the rs2276255 SNP on the risk of OPLL or OLF development [20], in contrast to Tanaka et al's finding of a weak significant effect (p = 0.048). Further contradiction in the COL6A1 gene is seen in Kong et al's (2007) finding that the promoter (−572) SNP T allele was associated with a 2.94 times greater risk of OPLL (p = 0.0003), while found no significant effect (p = 0.282) [22]. Liu et al (2010) found no effect of one additional SNP (rs9978314) on the risk of OPLL or OLF development [20].…”

“…Yan et al (2013) also found the Ser37Ala SNP to be associated with increased risk (p < 0.001) [21], although a more recent study that compared OPLL patients to their family members found no effect of either the Ser87Ser or Ser37Ala SNPs on risk of OPLL (p = 0.411, p = 0.670, respectively) [22]. Additionally, the 570A>T SNP in the BMP2 gene was not found to be significantly associated with risk of OPLL [21].…”

Genetics Underlying an Individualized Approach to Adult Spinal Disorders

“…Other studies have shown similar findings and linked this SNP to ossification of the ligamentum flavum and diffuse idiopathic skeletal hyperostosis (50, 51). However, a study of these COL6A1 SNPs in a Korean population revealed conflicting results (52). Although significant data support the two collagen molecules as contributing to the pathogenesis of OPLL, lack of data congruency has made reliable conclusions difficult to make, likely due to disease heterogeneity.…”

“…It is thought that distinct genetic characteristics define these seemingly similar, but quite clinically different syndromes. Our systematic review identified six works in the literature (Table 2) (52, 83–87) that identified genetic contributions for DS. The quality of the data is relatively limited (Level III studies) but provides some insight into potential genetic mechanisms for disease pathogenesis that could potentially be used in future studies.…”