Association of bone morphogenetic protein-2 gene polymorphisms with susceptibility to ossification of the posterior longitudinal ligament of the spine and its severity in Chinese patients

Abstract

A case–control study was conducted to examine the association between two single nucleotide polymorphisms (SNPs) in exon 2 of the bone morphogenetic protein-2 gene (BMP-2) and ossification of the posterior longitudinal ligament (OPLL), and to investigate whether SNPs of the Ser37Ala (T/G) and the Ser87Ser (A/G) in the BMP-2 gene are associated with genetic susceptibility to OPLL and its severity in Chinese subjects. The Ser87Ser (A/G) SNP has been implicated in bone mineral density (BMD) and increases the risk of OA in women. The Ser37Ala (T/G) SNP is associated with BMD and the rate of bone loss in osteoporosis and osteoporosis fractures. A total of 57 OPLL patients and 135 non-OPLL controls were studied. Radiographs of the cervical spine were analyzed to determine the presence and the severity of OPLL. The association of two SNPs with the occurrence and the extent of OPLL were statistically evaluated. There was a significant association between the Ser37Ala (T/G) polymorphism and the occurrence of OPLL in the cervical spine. However, no significant association was found between the Ser37Ala (T/G) polymorphism and the more number of ossified cervical vertebrae in OPLL patients. There was a significant association between the Ser87Ser (A/G) polymorphism and the more number of ossified cervical vertebrae in OPLL patients. However, there was no statistical difference between the Ser87Ser (A/G) SNP and the occurrence of OPLL in the cervical spine. In addition, the Ser87Ser (A/G) polymorphism in male patients and in female patients showed no statistical difference between cases and controls. The present results demonstrate that BMP-2 Gene is not only a factor associated with the occurrence of OPLL, but also a factor related to more extensive OPLL. The “G” allele in the Ser37Ala (T/G) polymorphism is associated with the occurrence of OPLL, but not more extensive OPLL in the cervical spine. The “G” allele in the Ser87Ser (A/G) polymorphism promotes the extent of OPLL, whereas the “A” allele in the Ser87Ser (A/G) polymorphism restricts ectopic ossification in the cervical spine at least in Chinese subjects.

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

“…Whereas this previous study used age-matched unaffected volunteers as the control group, the present study used unaffected family members of OPLL patients as the control. Although the frequencies of the "G" allele of BMP-2 Ser37Ala (T/G), the "T" allele of the COL6A1 promoter, and the "G" allele of COL6A1 intron 33 were similar to those reported in previous studies (Kong et al, 2007;Wang et al, 2008), unaffected family members in our study also exhibited similar allele frequencies (Table 2). This finding raises doubt as to the significance of these four SNPs for OPLL expression.…”

“…Genetic polymorphisms in several collagen genes (COL11A2 and COL6A1), which encode for extracellular matrix proteins, have been associated with OPLL (Tsukahara et al, 2005;Kong et al, 2007). The BMP-2 gene, which is a member of the TGF-b superfamily, acts as a potent stimulator of bone formation in vivo and has also been hypothesized to be involved in OPLL pathogenesis (Wang et al, 2008). Human nucleotide pyrophosphatase (NPPS) and its gene have been suggested to play a role in OPLL genetics (Nakamura et al, 1999).…”

“…Human nucleotide pyrophosphatase (NPPS) and its gene have been suggested to play a role in OPLL genetics (Nakamura et al, 1999). Wang et al (2008) and Kong et al (2007) reported that polymorphisms in BMP-2 and COL6A1 genes were associated with OPLL. Among these proposed candidate genes, we chose to further investigate the BMP-2 and COL6A1 genes to test our hypothesis that they are associated with OPLL in Korean patients and their unaffected family members.…”

“…Among these aforementioned genes of interest, the BMP-2 and COL6A1 genes were reported to be associated with OPLL in Japanese and Chinese Han populations, and were therefore selected for our study in a Korean population (Tanaka et al, 2003;Tsukahara et al, 2005;Kong et al, 2007;Wang et al, 2008). The primary aim of this study was to investigate the differences in genetic polymorphisms of BMP-2 and COL6A1 genes between OPLL patients and their family members (with and without OPLL).…”

Ossification of the posterior longitudinal ligament: a review

“…63 The TC and CC genotypes in exon 3(-726) T/C in the BMP-2 gene of male Han Chinese patients have a genetic susceptibility to OPLL in the cervical spine. 130 Wang et al 129 demonstrated an association between the Ser37Ala (T/G) polymorphism and the occurrence of OPLL. They also showed significant linkage between the Ser87Ser (A/G) polymorphism and the extent of cervical ossification.…”