Svetla Todorova NİKOLOVA, Vasil Tsankov YABLANSKİ, Evgeni Nedev VLAEV, Alexey Slavkov SAVOV, İvo Marinov KREMENSKY

Investigation of Predictive Potential of TPH1 Common Polymorphism in Idiopathic Scoliosis

Objectives: The association studies are the predominant type of studies on genetics of the common diseases. The present case-control study aims to investigate the association between the promoter polymorphism TPH1 (rs10488682 T/A) and the predisposition to idiopathic scoliosis (IS) in a Bulgarian population sample. Methods: A total of 105 patients and 210 healthy gender-matched controls were included. The TPH1 promoter polymorphism was genotyped by amplification followed by restriction. The statistical analysis was performed by the Pearson's chi-squared test and the Fisher’s exact test. A value of p less than 0.05 was considered statistically significant. Results: The results indicated that TPH1 (rs10488682) is not associated with the susceptibility to IS, the onset of the disease, the family history or the gender. Based on these preliminary results, the examined polymorphic variant could not be considered as a predisposing factor for IS in Bulgarian patients. Conclusions: Much larger case-control studies will be needed to examine the role of this TPH1 functional genetic variant in the etiology and pathogenesis of IS in Caucasian population. The identification of molecular markers for IS could be useful for early detection of the predisposition among the relatives and for more accurate prognosis of the risk for a rapid progression of the curve in the affected children.

Keywords:

Idiopathic, scoliosis, TPH1, polymorphism, association,

PDF

___

1. Patnala R, Clements J, Batra J. Candidate gene association studies: a comprehensive guide to useful in silico tools. BMC Genetics 2013; 14:39.
2. Kwon JM, Goate AM. The candidate gene approach. Alcohol Res Health 2000, 24(3):164-168.
3. Collins FS, Guyer MS, Chakravarti A. Variations on a theme: cataloging human DNA sequence variation. Science 1997; 278 (5343):1580-1581.
4. Peters BJM, Rodin AS, De Boer A, Maitland-van der Zee A-H. Methodological and statistical issues in pharmacogenomics. J Pharm Pharmacol 2010;62 (2):161–166.
5. Moreau A, Wang DS, Forget S, et al. Melatonin signaling dysfunction in adolescent idiopathic scoliosis. Spine 2004; 29:1772-81.
6. Machida M, Dubousset J, Imamura Y, et al. Pathogenesis of idiopathic scoliosis: sEPs in chicken with experimentally induced scoliosis and in patients with idiopathic scoliosis. J Pediatr Orthop 1994;14:329-35.
7. Machida M, Dubousset J, Imamura Y, Iwaya T, Yamada T, Kimura J. Role of melatonin deficiency in the development of scoliosis in pinealectomized chickens. J Bone Joint Surg Br. 1995; 77:134–8.
8. Kono H, Machida M, Saito M, et al. Mechanism of osteoporosis in adolescent idiopathic scoliosis: experimental scoliosis in pinealectomized chickens. J Pineal Res 2011; 51(4):387-93.
9. Cardinali D, Ladizesky M, Boggio V, Cutrera R, Mautalen EC. Melatonin Use as a Bone-Protecting Substance. In: Pandi-Perumal SR, Cardinali DP, editor. Melatonin: Biological Basis of its Function in Health and Disease, 2004.
10. Grivas TB, Savvidou OD. Melatonin the “light of night” in human biology and adolescent idiopathic scoliosis. Scoliosis 2007; 2:6.
11. Girardo M, Bettini N, Dema E, Cervellati S. The role of melatonin in the pathogenesis of adolescent idiopathic scoliosis (AIS). Eur Spine J 2011; 20(1):S68-S74.
12. Gorman KF, Julien C, Moreau A. The genetic epidemiology of idiopathic scoliosis. Europ Spine J 2012; 21(10):1905-1919.
13. Burger EL, Noshchenko A, Patel VV, Lindley EM, Bradford AP. Ultrastructure of Intervertebral Disc and Vertebra-Disc Junctions Zones as a Link in Etiopathogenesis of Idiopathic Scoliosis. Advanc Orthoped Surg 2014; 2014:850594.
14. Wang H, Wu Z, Zhuang Q, et al. Association study of tryptophan hydroxylase 1 and arylalkylamine Nacetyltransferase polymorphisms with adolescent idiopathic scoliosis in Han Chinese. Spine (Phila Pa1976) 2008; 33(20):2199-2203.
15. Takahashi Y, Matsumoto M, Karasugi T, et al. Lack of association between adolescent idiopathic scoliosis and previously reported single nucleotide polymorphisms in MATN-1, MTNR1B, TPH1, and IGF1 in a Japanese population. J Orthop Res 2011;29 (7):1055-1058.
16. Nelson LM, Ward K, Ogilvie JW. Genetic variants in melatonin synthesis and signaling pathway are not associated with adolescent idiopathic scoliosis. Spine (Phila Pa 1976) 2011; 36(1):37-40.
17. Altaf F. Adolescent Idiopathic Scoliosis. BMJ. 2013;346:f2508.
18. Ogilvie JW. Update on prognostic genetic testing in adolescent idiopathic scoliosis (AIS). Journal of Pediatric Orthopaedics. 2011; 31:S46-S48.
19. Qiu XS, Tang NL, Yeung HY, et al. The role of melatonin receptor 1B gene (MTNR1B) in adolescent idiopathic scoliosis–a genetic association study. Stud Health Technol Inform. 2006;123:3-128.
20. Qiu XS, Tang NL, Yeung HY, et al. Melatonin receptor 1B (MTNR1B) gene polymorphism is associated with the occurrence of adolescent idiopathic scoliosis. Spine (Phila Pa 1976) 2007;32(16):1748-1753.
21. Shyy W, Wang K, Gurnett CA, et al. Evaluation of GPR50, hMel-1B, and ROR-alpha melatoninrelated receptors and the etiology of adolescent idiopathic scoliosis. J Pediatr Orthop 2010;30(6):539-543.
22. Morocz M, Czibula A, Grozer ZB, et al. Association study of BMP4, IL6, Leptin, MMP3, and MTNR1B gene promoter polymorphisms and adolescent idiopathic scoliosis. Spine 2011; 36(2): E123–E130.
23. Nikolova S, Yablanski V, Vlaev E, Savov A, Kremensky I. Association study between idiopathic scoliosis and MTNR1B and CHD7 gene polymorphisms in Bulgarian patients. Science &Technologies: Medicine 2015; 5(1):81-86.