Journal of Pharmacy And Bioallied Sciences
Journal of Pharmacy And Bioallied Sciences Login  | Users Online: 610  Print this pageEmail this pageSmall font sizeDefault font sizeIncrease font size 
    Home | About us | Editorial board | Search | Ahead of print | Current Issue | Past Issues | Instructions | Online submission




 
 Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 11  |  Issue : 6  |  Page : 457-462  

Assessment of correlation of growth hormone receptor gene with tooth dimensions: A CBCT and genotyping study


1 Department of Pedodontics and Preventive Dentistry, SMBT Dental College and Hospital, Sangamner, Maharashtra, India
2 Department of Periodontology, Vaidik Dental College and Research Centre, Daman, Daman and Diu, India
3 Department of Oral Medicine and Radiology, Vyws Dental College and Hospital, Amravati, Maharashtra, India
4 Department of Oral Medicine and Radiology, R.R. Kambe dental college, Akola, Maharashtra, India
5 Department of Periodontics, R.R. Kambe dental college, Akola, Maharashtra, India
6 Department of Orthodontics and Dentofacial Orthopedics, Rural Dental College, Pravara Institute of Medical Sciences, Loni, Maharashtra, India

Date of Web Publication28-May-2019

Correspondence Address:
Dr. Gaurav Ramdhan Shinde
Department of Pedodontics and Preventive Dentistry, SMBT Dental College and Hospital, Sangamner 422608, Maharashtra
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JPBS.JPBS_76_19

Rights and Permissions
   Abstract 

Aim: Assessment of root morphology, size, and amount of bone around tooth is essential before starting the orthodontic treatment. The present study aimed to assess the relationship between tooth dimensions with two gene variants of growth hormone (GH), namely rs6184 and rs6180. Materials and Methods: This study was conducted on 218 subjects (males: 104, females: 114) requiring orthodontic treatment. All underwent cone beam computed tomography (CBCT) scan for orthodontic treatment planning with Kodak CBCT machine. In all teeth, crown height (CH), root length (RL), and crown–root ratio were evaluated. Two growth hormone receptor (GHR) variants (rs6184 and rs6180) were genotyped using the TaqMan genotyping assay. Results: The mean CH and RL of all teeth, that is, maxillary and mandibular central incisors, lateral incisor, canine, first premolar, second premolar, first molar, and second molar, were measured. There was no significant difference in males and females (P > 0.05). Allele frequencies of GHR variants for rs6180 and rs6184 were 48.1% and 8.92%, respectively. Multiple regression analysis showed GHR rs6184 association with maxillary central incisor CH, maxillary canine RL, mandibular canine CH, and mandibular first premolar RL (P < 0.05). Conclusion: There was correlation of CH of maxillary and mandibular canine and RL of maxillary canine and mandibular first premolar with GHR rs6184.

Keywords: Growth hormone, mandibular, maxillary, teeth


How to cite this article:
Shinde GR, Mhaisekar RD, Chaube SH, Barad AN, Bhadange S, Patel HJ. Assessment of correlation of growth hormone receptor gene with tooth dimensions: A CBCT and genotyping study. J Pharm Bioall Sci 2019;11, Suppl S2:457-62

How to cite this URL:
Shinde GR, Mhaisekar RD, Chaube SH, Barad AN, Bhadange S, Patel HJ. Assessment of correlation of growth hormone receptor gene with tooth dimensions: A CBCT and genotyping study. J Pharm Bioall Sci [serial online] 2019 [cited 2019 Jun 18];11, Suppl S2:457-62. Available from: http://www.jpbsonline.org/text.asp?2019/11/6/457/258893




   Introduction Top


Facial esthetics is of great concern not only in young but in old too. With the advancement in the field of orthodontics, various techniques have been emerged, leading to correction of skeletal and dental anomalies. For the application of orthodontic forces, there should be adequate crown structure. Type of malocclusion determines the type of force as well as area from which force has to be given.[1]

A significantly acceptable crown–root ratio is necessary for obtaining good results. Assessment of root morphology, and size and amount of bone around tooth are essential before starting the orthodontic treatment. Studies have revealed genetic and environmental factors as causative factors for tooth and skeletal anomalies.[2],[3]

A study conducted by Kimura et al.[4] has demonstrated common variation in EDAR as a genetic determinant of shovel-shaped incisors in study group. Genetics has been considered as one of the important factors of dental and skeletal anomalies. Similarly, another study by Kimura et al.[5] suggested the role of polymorphisms in WNT10A in tooth morphology as well as hair shape.

The presence of hypoconulid in mandibular second molar, accessory cusp in mandibular second premolar, and cusp of carabelli in maxillary first molar is considered as a result of genetic predisposition. Growth hormone (GH) is responsible for postnatal growth with GH/GHR/insulinlike growth factor 1 signaling axis. Van et al.[6] showed that GH is required for normal tooth eruption and maturation. Thus, there is great need of such studies that may depict the role of genetics in assessing dental anomalies. This study was conducted to assess the relationship between tooth dimensions with two gene variants of GH, namely rs6184 and rs6180.

[TAG:2]Materials and Methods[/TAG:2]

This study was conducted in the Department of Pedodontics and Preventive Dentistry, SMBT Dental College and Hospital, Sangamner, Maharashtra, India. It comprised 218 subjects (males: 104, females: 114) requiring orthodontic treatment. All participants were informed regarding the study and written consent was obtained. Ethical clearance was obtained prior to commencement of study from ethical committee.

Inclusion criteria included patients aged 14–22 years and patients without history of trauma. Exclusion criteria were patients with congenital tooth and skeletal anomalies, orthodontic history, and poor-quality radiographs.

General information such as name, age, and gender was recorded in case history pro forma. All underwent cone beam computed tomography (CBCT) scan for orthodontic treatment planning with a Kodak CBCT machine operating at 80 kVp, 5 mA, and 18 second exposure time. Multiplanar reconstruction was performed and all the planes such as axial, coronal, and sagittal were obtained [Figure 1], [Figure 2], [Figure 3]. For assessment of crown height (CH), a line joining the mesial and distal cementoenamel junction was measured. The length was measured between crown tip and this line. For root length (RL), the measurement between cervical line and root tip, was considered [Figure 4] and [Figure 5]. Measurements of all teeth were performed and overall tooth dimension was calculated by adding CH with RL. Crown–root ratio was evaluated by dividing CH with RL.
Figure 1: Axial plane

Click here to view
,
Figure 2: Coronal plane

Click here to view
,
Figure 3: Sagittal plane

Click here to view
,
Figure 4: Measurements (CH, canine height; RL, root length)

Click here to view
,
Figure 5: Measurements (CH, canine height; RL, root length)

Click here to view


Two independent oral and maxillofacial radiologists performed all the measurements and average of both findings was considered to eliminate bias. All the measurements were performed with OsiriX CBCT software.

For genotyping, unstimulated saliva of subjects was collected in a saliva collector and stored at room temperature. Genomic DNA was extracted from the saliva samples. Two growth hormone receptor (GHR) variants (rs6184 and rs6180) were genotyped using the TaqMan genotyping assay. Results thus obtained were subjected to statistical analysis. P value less than 0.05 was considered significant.


   Results Top


[Table 1] and [Graph 1] show that there are 104 (47.7%) males and 114 (52.3%) females. [Table 2] and [Graph 2] show mean CH and RL of all teeth, that is, maxillary central incisor, lateral incisor, canine, first premolar, second premolar, first molar, and second molar. There is no significant difference between males and females (P > 0.05).
Table 1: Distribution of subjects

Click here to view
,
Graph 1: Distribution of subjects

Click here to view
,
Table 2: Measurements of maxillary teeth

Click here to view
,
Graph 2: Measurements of maxillary teeth

Click here to view


[Table 3] and [Graph 3] show mean CH and RL of all teeth, that is, mandibular central incisor, lateral incisor, canine, first premolar, second premolar, first molar, and second molar. There is no significant difference in males and females (P > 0.05).
Table 3: Measurements of mandibular teeth

Click here to view
,
Graph 3: Measurements of mandibular teeth

Click here to view


[Table 4] shows that allele frequencies of GHR variants for rs6180 and rs6184 are 48.1% and 8.92%, respectively. [Table 5] shows that multiple regression analysis indicates association of GHR rs6184 with maxillary central incisor CH, maxillary canine RL, mandibular canine CH, and mandibular first premolar RL (P < 0.05).
Table 4: Single nucleotide polymorphism

Click here to view
,
Table 5: Association tests using multiple regression analyses

Click here to view



   Discussion Top


In orthodontics, the size of tooth, that is, crown length and RL, plays an important role. GH is essential for tooth eruption and maturation. It has been found that in dwarfism, there is a small-sized tooth whereas in the case of gigantism, there is an enlarged tooth.[7] Campbell et al.[8] revealed that GH mutation is the leading cause of delayed tooth eruption and maturation. In present study, we assessed the relationship between tooth dimensions with two gene variants of GH, namely rs6184 and rs6180.

In this study, we included 218 subjects requiring orthodontic treatment of both genders. In all subjects, genotyping of two GHR variants (rs6184 and rs6180) was performed using the TaqMan genotyping assay. CBCT scan of all teeth was conducted.

Tomoyasu et al.[9] performed a study to find out the association between mandibular height and the GHR gene in study population. The authors found a strong correlation between mandibular ramus height and GHR gene. Similarly, a study performed by Kang et al.[10] found an association of the GHR gene polymorphisms with mandibular height. The distance between the left and right condyles and coronoid process was assessed to find its relation with GHR.

In this study, we evaluated CH and RL as well as crown–root ratio. We observed that there was no significant difference in CH, RL, and crown–root ratio of maxillary and mandibular teeth.

It has been postulated that the formation and eruption of teeth are greatly affected by cell sensitivity of GH and the site of GH action.[11] At sites of new matrix formation, cementoblasts and odontoblasts displayed expression specifically against GHR, although cementocytes and mature odontoblasts at later stages of tooth development did not. The functional mechanism by which the GHR gene variant identified may be responsible for tooth length is still unclear.[12]

We found that mean CH of maxillary central incisor in males was 10.12mm and in females was 10.11mm; the RL was 13.24mm in males and 13.20mm in females. In lateral incisors, the mean CH was 10.04 and 10.02mm in males and females, respectively, whereas RL was 12.18 and 12.19mm, respectively. In canine, CH was 11.12 and 11.21mm and RL was 15.42 and 15.32mm in males and females, respectively. Our results are in agreement with those of Smith et al.[13]

Maxillary first premolar showed mean CH as 9.02mm in males and 9.04mm in females, and RL as 11.31mm in males and 11.25mm in females; second premolar showed CH as 8.76mm in males and 8.65mm in females, and RL as 11.20mm in males and 11.25mm in females. Maxillary first molar showed CH as 8.54mm in males and 8.51 in females, and RL as 10.08 in males and 10.16mm in females. Maxillary second molar showed CH as 8.34mm in males and 8.41mm in females whereas RL was 10.12 and 10.19mm in males and females, respectively.

We found that mean CH of mandibular central incisor in males was 8.14mm and in females was 8.01mm; the RL was 12.10mm in males and 12.23mm in females. In lateral incisors, the mean CH was 9.12 and 9.23mm in males and females, respectively, whereas RL was 12.05 and 12.21mm. In canine, CH was 10.21 and 10.14mm, and RL was 15.88 and 14.36mm in males and females, respectively.

Mandibular first premolar showed mean CH as 9.32mm in males and 8.04mm in females, and RL as 13.34mm in males and 12.21mm in females; second premolar showed CH as 8.24mm in males and 8.15mm in females, and RL as 13.22mm in males and 13.25mm in females. Mandibular first molar showed CH as 8.44mm in males and 8.58mm in females, RL as 10.28mm in males and 10.12mm in females. Mandibular second molar showed CH as 7.29mm in males and 8.47mm in females whereas RL was 11.85 and 11.22mm in males and females, respectively. This is similar to the results of the study by Pentinpuro et al.[14]

In this study, we found correlation of GHR rs6184 with maxillary central incisor CH, maxillary canine RL, mandibular canine CH, and mandibular first premolar RL. This is in agreement with the results of the study by Hikita et al.[15] The authors found relationship of GHR variant rs6184 with RLs and tooth length for the upper and lower lateral incisors and upper canines.

We found allele frequencies of GHR variants for rs6180 and rs6184 as 48.1% and 8.92%, respectively. Similarly, Hikita et al.[15] found 46.6% and 8.1% allele frequencies of GHR variants for rs6180 and rs6184.

In this study, CBCT was selected as a radiological tool because it offers better results in terms of providing three dimensions and accurate measurements compared to conventional two-dimensional radiographs. It offers less patient exposure than CT and hence useful in this study. A limitation of this study was limited patient size.


   Conclusion Top


We found correlation of CH of maxillary and mandibular canine and RL of maxillary canine and mandibular first premolar with GHR rs6184. Large-scale future studies are required to support the results of the present study. GHR gene assessment may predict tooth maturation and development.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Marques LS, Generoso R, Armond MC, Pazzini CA. Short-root anomaly in an orthodontic patient. Am J Orthod Dentofacial Orthop 2010;138:346-8.  Back to cited text no. 1
    
2.
Kamble RH, Lohkare S, Hararey PV, Mundada RD. Stress distribution pattern in a root of maxillary central incisor having various root morphologies: A finite element study. Angle Orthod 2012;82:799-805.  Back to cited text no. 2
    
3.
Lombardo L, Scuzzo G, Arreghini A, Gorgun O, Ortan YO, Siciliani G. 3D FEM comparison of lingual and labial orthodontics in en masse retraction. Prog Orthod 2014;15:38.  Back to cited text no. 3
    
4.
Kimura R, Yamaguchi T, Takeda M, Kondo O, Toma T, Haneji K, et al. A common variation in EDAR is a genetic determinant of shovel-shaped incisors. Am J Hum Genet 2009;85:528-35.  Back to cited text no. 4
    
5.
Kimura R, Watanabe C, Kawaguchi A, Kim YI, Park SB, Maki K, et al. Common polymorphisms in WNT10A affect tooth morphology as well as hair shape. Hum Mol Genet 2015;24:2673-80.  Back to cited text no. 5
    
6.
Van Erum R, Mulier G, Carels C, de Zegher F. Craniofacial growth and dental maturation in short children born small for gestational age: Effect of growth hormone treatment. Own observations and review of the literature. Horm Res 1998;50:141-6.  Back to cited text no. 6
    
7.
Lee WC, Yamaguchi T, Watanabe C, Kawaguchi A, Takeda M, Kim YI, et al. Association of common PAX9 variants with permanent tooth size variation in non-syndromic East Asian populations. J Hum Genet 2012;57:654-9.  Back to cited text no. 7
    
8.
Campbell R, Weinshel R, Backeljauw P, Wilson S, Bean J, Shao M. Dental development in children with growth hormone insensitivity syndrome: Demirjian analysis of serial panoramic radiographs. Cleft Palate Craniofac J 2009;46:409-14.  Back to cited text no. 8
    
9.
Tomoyasu Y, Yamaguchi T, Tajima A, Nakajima T, Inoue I, Maki K. Further evidence for an association between mandibular height and the growth hormone receptor gene in a Japanese population. Am J Orthod Dentofacial Orthop 2009;136:536-41.  Back to cited text no. 9
    
10.
Kang EH, Yamaguchi T, Tajima A, Nakajima T, Tomoyasu Y, Watanabe M, et al. Association of the growth hormone receptor gene polymorphisms with mandibular height in a Korean population. Arch Oral Biol 2009;54:556-62.  Back to cited text no. 10
    
11.
Sasaki Y, Satoh K, Hayasaki H, Fukumoto S, Fujiwara T, Nonaka K. The P561T polymorphism of the growth hormone receptor gene has an inhibitory effect on mandibular growth in young children. Eur J Orthod 2009;31:536-41.  Back to cited text no. 11
    
12.
Nakawaki T, Yamaguchi T, Isa M, Kawaguchi A, Tomita D, Hikita Y, et al. Growth hormone receptor gene variant and three-dimensional mandibular morphology. Angle Orthod 2017;87:68-73.  Back to cited text no. 12
    
13.
Smith P, Wax Y, Adler F. Population variation in tooth, jaw, and root size: A radiographic study of two populations in a high-attrition environment. Am J Phys Anthropol 1989;79:197-206.  Back to cited text no. 13
    
14.
Pentinpuro RH, Lähdesmäki RE, Niinimaa AO, Pesonen PR, Alvesalo LJ. Crown heights in the permanent teeth of 45, X and 45, X/46, XX females. Acta Odontol Scand 2014;72:908-16.  Back to cited text no. 14
    
15.
Hikita Y, Yamaguchi T, Tomita D, Adel M, Nakawaki T, Katayama K, et al. Growth hormone receptor gene is related to root length and tooth length in human teeth. Angle Orthod 2018;88:575-81.  Back to cited text no. 15
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Graph 1], [Graph 2], [Graph 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

Top
 
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
    Abstract
   Introduction
   Materialsand Methods
   Results
   Discussion
   Conclusion
    References
    Article Figures
    Article Tables

 Article Access Statistics
    Viewed38    
    Printed0    
    Emailed0    
    PDF Downloaded3    
    Comments [Add]    

Recommend this journal