Association between cSNPs of BMP2 Gene and Degenerative Lumbar Scoliosis in Korean Population

Research Article

J Fam Med. 2014;1(2): 5.

Association between cSNPs of BMP2 Gene and Degenerative Lumbar Scoliosis in Korean Population

Hyung-Ki Kim1, Hwayoung Lee1, Jun-Tack Kwon1, Ki Tack Kim2, Hak-Jae Kim1,3*

1Department of Clinical Pharmacology, Soonchunhyang University, Republic of Korea

2Department of Orthopedic Surgery, Kyung Hee University East West Neomedical Center, Republic of Korea

3Soonchunhyang Medical Research Institute, Soonchunhyang University, Cheonan, Republic of Korea

*Corresponding author: Hak-Jae Kim, Department of Clinical Pharmacology, College of Medicine, Soonchunhyang University, Republic of Korea

Received: July 31, 2014; Accepted: October 28, 2014; Published: October 29, 2014


Background: Bone morphogenetic proteins (BMPs) are involved in cartilage and bone formation. However, the association between single nucleotide polymorphisms (SNPs) of BMP genes and degenerative lumbar scoliosis (DLS) has not been investigated yet. The aim of this study was to determine whether coding SNPs (cSNPs) of BMP genes (BMP2, 3, 4, 5, 6, and 10) are associated with DLS in Korean population.

Methods: Seven cSNPs in BMP genes were selected and genotyped for 66 patients with DLS and 127 healthy controls using direct sequencing.

Results: Of the SNPs examined, two cSNPs of BMP2 gene showed weak associations with DLS in the codominant (rs235768, Arg190Ser, missense, OR = 2.28, 95% CI = 1.19 – 4.36, p = 0.03) and dominant models (rs235768, OR = 1.99, 95% CI = 1.07 – 3.72, p = 0.03; rs1049007, Ser87Ser, synonymous, OR = 1.93, 95% CI = 1.039 – 3.62, p = 0.04).

Conclusion: BMP2 may be a susceptible gene for DLS in Korean population.


Lumbar scoliosis is a three-dimensional deformity of spine associated with structural alterations of vertebral bodies. Lumbar scoliosis in adult stage could be from deformity developed at growing age or de novo degenerative deformity after skeletal maturity [1-6]. Degenerative lumbar scoliosis (DLS), “de novo”” lumbar scoliosis, usually occurs after the fourth or fifth decade in patients without history of scoliosis. The curve is composed of a few vertebral bodies with its apex in the intervertebral space, most frequently at the L2 - L3 or the L3 - L4 level [7-9]. The causes of DLS development are various. Degeneration of the spinal column is the most common cause. Neuromuscular disorders, metabolic abnormalities (osteoporosis), leg length discrepancy, long-standing pelvic obliquity, and outcomes of prior surgical interventions are other causes [10]. Several genetic variations have been linked to lumbar spine degeneration or osteoporosis [11, 12]. Intra genic polymorphisms of vitamin D receptor gene were reported to be associated with lumbar spine degeneration and bone density [11]. G�mez et al. (2007) reported that estrogen receptor alpha gene polymorphisms were associated with osteoporosis [12].

Bone morphogenetic proteins (BMPs) are phylogenetically conserved signaling growth factors belonging to the transforming growth factor beta super family [13-15]. BMPs also play important roles in the pathophysiology of several diseases, including osteoporosis [16], arthritis [17], pulmonary hypertension [17, 18], and kidney diseases [19]. Previous studies have reported that BMPs (BMP2, BMP6, BMP7, and BMP15) are associated with several diseases such as ossification of the posterior longitudinal ligament (OPLL), a vascular necrosis, and ovarian failure [20-26]. Wang et al. (2008) reported a positive association between BMP2 polymorphisms [Ser37Ala (T/G) and Ser87Ser (A/G)] and OPLL of the cervical spine.

Despite the potentially important role of BMPs in the development of DLS, the association between genetic variations of BMPs and DLS has not been reported. Therefore, the objective of this study was to determine whether coding single nucleotide polymorphisms (cSNPs) of BMP family genes (BMP2, 3, 4, 5, 6, and 10) are associated with DLS in Korean population



All patients with DLS were from Kyung Hee University East- West Neo-Medical Center, Seoul, Republic of Korea and National Medical Center, Seoul, Republic of Korea. The DLS group included 66 patients with mean age of 69.1 ± 7.7 years (7 male, 65.4 ± 8.1 years; 59 female, 69.6 ± 7.6 years). The control group was recruited after it was confirmed in a general health check-up program that they had no clinical evidence of DLS or any other disorders. A total of 127 healthy controls with mean age of 68.1 ± 8.6 years (17 male, 71.6 ± 8.3 years; 110 female, 67.5 ± 8.6 years) were recruited. All case-control subjects used in this study were surveyed through the same center. Each patient was diagnosed by a special spine surgeon. All patients fulfilled physical examination and radiographic criteria (Cobb’s angle over 10 degrees) [27]. Informed consent was obtained from all individuals according to the Declaration of Helsinki guidelines [28]. The study was approved by the ethics review committee of the Medical Research Institute, Kyung Hee University Medical Center, Seoul, Republic of Korea.

SNP Genotyping

First, we searched for cSNPs of BMP genes originally known as “BMP” (BMP2/3/4/5/6/8/10/15) in GenBank database (https://www. The SNPs of procollagen C-proteinase (PCP, same as BMP1), osteogenic protein 1 (OP1, same as BMP7), and GDF2/5/6/7/11 (same as BMP9/14/13/12/11) genes were excluded from this study. Related information of cSNP sequences was obtained from the SNP database (dbSNP #130) of the National Center for Biotechnology Information (NCBI). The SNPs with unknown heterozygosity and minor allele frequency (below 5%) were excluded. Finally, rs235768 (BMP2), rs1049007 (BMP2), rs3733549 (BMP3),rs17563 (BMP4), rs3734444 (BMP5), rs17557 (BMP6), and rs2231344 (BMP10) were selected.

Genomic DNA was extracted from blood samples collected in EDTA using a commercially available Qiagen DNA Extraction kit (Qiagen, Tokyo, Japan). Genomic DNA was amplified using the genespecific primers for each SNP (Table 1). PCR products were sequenced using ABI PRISM 3730XL analyzer (PE Applied Biosystems, Foster City, California, USA). Sequence data were analyzed using SeqManII software (DNASTAR Inc., Madison, WI, USA).