RANKL Gene Polymorphism rs9594738 in Cases of Malocclusion Due to Persistence of Primary Teeth in Minangkabau Children

Abstract

Objective

Malocclusion is an important dental health problem, especially in children. One factor causing malocclusion is the persistence of primary teeth, which genetic factors can influence. This study provides a new understanding of the role of genetics in causing malocclusion and its impact on preventive planning and orthodontic treatment.

Materials and Methods

This was an observational analytic study with a cross-sectional research design. The research subjects were children of SD Pembangunan UNP Padang, Minangkabau tribe, aged 6 to 13 years, a total of 30 people, consisting of a case group and a control group. Saliva was collected using a nonstimulated method (passive salivation). The polymorphism of the RANKL rs9594738 gene was analyzed using the polymerase chain reaction-restriction fragment length polymorphism method. Amplification results were analyzed via agarose gel electrophoresis to determine genotype. Data analysis was performed using the chi-square test.

Results

RANKL rs9594738 gene polymorphism in the case group was higher than in the control group. The chi-square test shows an association between RANKL rs9594738 gene polymorphism and dental malocclusion due to the persistence of primary teeth.

Conclusion

The data shows that the RANKL rs9594738 gene polymorphism is associated with dental malocclusion due to the persistence of primary teeth. The occurrence of malocclusion due to the persistence of primary teeth is a multigenetic phenomenon. In addition to the RANKL gene, osteoprotegerin, and matrix metalloproteinases, other genes that affect the replacement of primary teeth to permanent teeth are colony-stimulating factor 1, tumor necrosis factor ligand superfamily member 11, runt-related transcription factor 2, interleukin-1β, cathepsin K, sclerostin, and parathyroid hormone.

Keywords

permanent dental malocclusion - primary tooth persistence - RANKL gene polymorphism rs9594738 - primary tooth resorption - DNA sequencing and electrophoresis

Ethical Approval

Ethical approval for this study was obtained from the Ethics Committee of the Faculty of Medicine, ANDALAS University, West Sumatera, Indonesia (Approval No. 267/UN.16.2/KEP-FK/2023).

Publication History

Article published online:
18 August 2025

• References

• 1 Proffit WR. Contemporary Orthodontics. St. Louis, MO: Elsevier/Mosby; ; c2013; 2018
• 2 Petean IBF, Küchler EC, Soares IMV. et al. Genetic polymorphisms in RANK and RANKL are associated with persistent apical periodontitis. J Endod 2019; 45 (05) 526-531
• 3 Arid J, Xavier TA, da Silva RAB. et al. RANKL is associated with persistent primary teeth and delayed permanent tooth emergence. Int J Paediatr Dent 2019; 29 (03) 294-300
• 4 Djuwita R, Purwantyastuti P, Kamso S. Nutrients intake pattern of a Minangkabau ethnic group. Makara J Health Res 2010; 7 (01) 7-11
• 5 Küchler EC, Schröder A, Corso P. et al. Genetic polymorphisms influence gene expression of human periodontal ligament fibroblasts in the early phases of orthodontic tooth movement. Odontology 2020; 108 (03) 493-502
• 6 Hovorakova M, Lesot H, Peterka M, Peterkova R. Early development of the human dentition revisited. J Anat 2018; 233 (02) 135-145
• 7 Vanka A, Sadaka Alsindi R, Fouad Alyaqoub R. et al. Dental malocclusion impact on self-esteem levels among teenagers: life sciences -dentistry. Int J Life Sci Pharma Res 2023; 13 (05) 311-315
• 8 Dimberg L, Lennartsson B, Arnrup K, Bondemark L. Prevalence and change of malocclusions from primary to early permanent dentition: a longitudinal study. Angle Orthod 2015; 85 (05) 728-734
• 9 Hienz SA, Paliwal S, Ivanovski S. Mechanisms of bone resorption in periodontitis. J Immunol Res 2015; 2015: 615486
• 10 Tu P, Duan P, Zhang RS. et al. Polymorphisms in genes in the RANKL/RANK/OPG pathway are associated with bone mineral density at different skeletal sites in post-menopausal women. Osteoporos Int 2015; 26 (01) 179-185
• 11 Roshandel D, Holliday KL, Pye SR. et al; EMAS Study Group. Genetic variation in the RANKL/RANK/OPG signaling pathway is associated with bone turnover and bone mineral density in men. J Bone Miner Res 2010; 25 (08) 1830-1838
• 12 Al-Gunaid TH, Arifin R, Narmada IB, Tarman KE. Perspectives of indonesian orthodontists on the ideal orthodontic treatment time. Clin Cosmet Investig Dent 2020; 12: 351-357
• 13 Deng J, Zhuang ZM, Xu X, Han B, Song GY, Xu TM. Mechanical force increases tooth movement and promotes remodeling of alveolar bone defects augmented with bovine bone mineral. Prog Orthod 2024; 25 (01) 2
• 14 Loos BG, Van Dyke TE. The role of inflammation and genetics in periodontal disease. Periodontol 2000 2020; 83 (01) 26-39
• 15 Thorisson GA, Stein LD. The SNP Consortium website: past, present and future. Nucleic Acids Res 2003; 31 (01) 124-127
• 16 Clifford RJ, Edmonson MN, Nguyen C, Scherpbier T, Hu Y, Buetow KH. Bioinformatics tools for single nucleotide polymorphism discovery and analysis. Ann N Y Acad Sci 2004; 1020: 101-109
• 17 Franco C, Patricia HR, Timo S, Claudia B, Marcela H. Matrix metalloproteinases as regulators of periodontal inflammation. Int J Mol Sci 2017; 18 (02) 1-12
• 18 Jang DI, Lee AH, Shin HY. et al. The role of tumor necrosis factor alpha (Tnf-α) in autoimmune disease and current tnf-α inhibitors in therapeutics. Int J Mol Sci 2021; 22 (05) 1-16
• 19 MacLeod RS, Meyer MB, Xiong J. et al. Deletion of a putative promoter-proximal Tnfsf11 regulatory region in mice does not alter bone mass or Tnfsf11 expression in vivo. PLoS One 2021; 16 (05) e0250974
• 20 Qin X, Jiang Q, Nagano K. et al. Runx2 is essential for the transdifferentiation of chondrocytes into osteoblasts. PLoS Genet 2020; 16 (11) e1009169
• 21 Klein Y, David E, Pinto N, Khoury Y, Barenholz Y, Chaushu S. Breaking a dogma: orthodontic tooth movement alters systemic immunity. Prog Orthod 2024; 25 (01) 38
• 22 Famutimi OG, Adebiyi VG, Akinmolu BG, Dada OV, Adewale IO. Trypsin, chymotrypsin and elastase in health and disease. Futur J Pharm Sci 2024; 10: 126
• 23 van Dinther M, Zhang J, Weidauer SE. et al. Anti-sclerostin antibody inhibits internalization of sclerostin and sclerostin-mediated antagonism of Wnt/LRP6 signaling. PLoS One 2013; 8 (04) e62295
• 24 O'Brien CA, Plotkin LI, Galli C. et al. Control of bone mass and remodeling by PTH receptor signaling in osteocytes. PLoS One 2008; 3 (08) e2942