Osteopontin, Bone Morphogenetic Protein-4, and Vitamin D Receptor Gene Polymorphisms in the Susceptibility and Clinical Severity of Spinal Tuberculosis

骨桥蛋白、骨形态发生蛋白-4 和维生素 D 受体基因多态性与脊柱结核易感性和临床严重程度的关系

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作者:Guohua Wang, Liangyi Xie, Jianzhong Hu, Hongbin Lu, Xiangyang Liu, Yong Cao, Bin Liu, Yi Zhang, Xiongjie Shen

Aims

Spinal tuberculosis (TB) is a common and dangerous form of extrapulmonary TB with unclear mechanisms in its occurrence and progression. This study investigated the clinical significances of bone morphogenetic protein-4 (BMP-4), osteopontin (OPN), and vitamin D receptor (VDR) gene polymorphism, mRNA and protein expression in spinal TB patients.

Background/aims

Spinal tuberculosis (TB) is a common and dangerous form of extrapulmonary TB with unclear mechanisms in its occurrence and progression. This study investigated the clinical significances of bone morphogenetic protein-4 (BMP-4), osteopontin (OPN), and vitamin D receptor (VDR) gene polymorphism, mRNA and protein expression in spinal TB patients.

Conclusion

The 6007C>T polymorphism of BMP-4, -66T>G polymorphism of OPN, and VDR-FokI polymorphism are the susceptible factors of spinal TB and indicators of the clinical severity. These three genes may collaborate in the development of spinal TB.

Methods

BMP-4 and OPN gene polymorphisms were detected by direct DNA sequencing, while VDR-FokI polymorphisms were analyzed using PCR-RFLP. mRNA and protein expression was measured using real-time PCR and Western blot, respectively.

Results

A significant lower frequency of TT genotype and T allele at 6007C>T polymorphism in BMP-4 gene; higher frequency of GG genotype and G allele at -66T>G polymorphism in OPN gene, and higher frequency of the ff genotype and f allele at the VDR-FokI polymorphism were observed in patients with spinal TB compared to controls. TT genotype of 6007C>T polymorphism correlated with a lower BMP-4 mRNA and protein expression, -66GG genotype correlated with a high OPN mRNA and protein expression, and ff genotype correlated with the lower VDR mRNA and protein levels in the intervertebral disc tissues. The TT genotype and low BMP-4 gene expression; the -66GG genotype and high OPN gene expression; and the ff genotype and low VDR gene expression significantly correlated with the clinical severity of spinal TB.

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