The aim of this study was to evaluate the association between genetic polymorphisms in RANK, RANKL and OPG with maxillary and mandibular dimensions in humans.
Design
DNA extracted from saliva and the rs3826620, rs9594738 and rs2073618 polymorphisms in RANK, RANKL and OPG, respectively, were analysed by real-time PCR. Four linear measurements (Co-Gn, GoPg, Co-Go and PTM–A) from lateral cephalograms were examined for the evaluation of craniofacial measurements. ANOVA testing and a multivariate linear regression analysis, adjusted for age and gender, were used for statistical analysis, with an alpha of 5%. Hardy-Weinberg equilibrium was also evaluated using the chi-square test within each polymorphism.
Setting
School of Dentistry of Ribeirão Preto, University of São Paulo.
Participants
A total of 100 unrelated non-syndromic Brazilian Caucasian subjects were included in this study.
Results
The polymorphism in RANK was associated with a higher Go-Pg measurement (p = .039). In the multivariate analysis, adjusted for age and gender, the polymorphism in RANK was associated with Go-Pg (p = .017) and Co-Gn (p = .043).
Conclusion
The polymorphism rs3826620 in RANK is associated with the mandibular size.
Appelman-DijkstraNM, PapapoulosSE. 2016. From disease to treatment: from rare skeletal disorders to treatments for osteoporosis. Endocrine. 52:414–426.
2.
ArunRM, LakkakulaBV, ChitharanjanAB. 2016. Role of myosin 1H gene polymorphisms in mandibular retrognathism. Am J Orthod Dentofacial Orthop. 149:699–704.
3.
AttanasioC, NordAS, ZhuY, BlowMJ, LiZ, LibertonDK, MorrisonH, Plajzer-FrickI, HoltA, HosseiniR, et al.2013. Fine tuning of craniofacial morphology by distant-acting enhancers. Science. 342:1241006.
4.
BayramS, BasciftciFA, KurarE.2014. Relationship between P561T and C422F polymorphisms in growth hormone receptor gene and mandibular prognathism. Angle Orthod. 84:803–809.
5.
BoyceBF, XingL.2008. Functions of RANKL/RANK/OPG in bone modeling and remodeling. Arch Biochem Biophys. 473:139–146.
6.
Da FontouraCS, MillerSF, WehbyGL, AmendtBA, HoltonNE, SouthardTE, AllareddyV, Moreno uribeLM. 2015. Candidate gene analyses of skeletal variation in malocclusion. J Dent Res. 94:913–920.
GuanX, SongY, OttJ, ZhangY, LiC, XinT, LiZ, GanY, LiJ, ZhouS, ZhouY.2015. The ADAMTS1 gene Is associated with familial mandibular prognathism. J Dent Res. 94:1196–1201.
9.
HorowitzS, OsborneR, DegeorgeF.1960. A cephalometric study of craniofacial variation in adult twins. Angle Orthodontist. 30:1–5.
10.
HunterWS. 1965. A study of the inheritance of craniofacial characteristics as seen in lateral cephalograms of 72 like-sexed twins. Rep Congr Eur Orthod Soc. 41:59–70.
11.
HunterWS, BalbachDR, LamphiearDE. 1970. The heritability of attained growth in the human face. Am J Orthod. 58:128–134.
12.
KangEH, YamaguchiT, TajimaA, NakajimaT, TomoyasuY, WatanabeM, YamaguchiM, ParkSB, MakiK, InoueI.2009. Association of the growth hormone receptor gene polymorphisms with mandibular height in a Korean population. Arch Oral Biol. 54:556–562.
13.
KivirantaR, MorkoJ, AlataloSL, NicamhlaoibhR, RisteliJ, Laitala-LeinonenT, VuorioE.2004. Impaired bone resorption in cathepsin K-deficient mice is partially compensated for by enhanced osteoclastogenesis and increased expression of other proteases via an increased RANKL/OPG ratio. Bone. 36:159–172.
14.
KlingenbergCP, LeamyLJ, CheverudJM. 2004. Integration and modularity of quantitative trait locus effects on geometric shape in the mouse mandible. Genetics. 166:1909–1921.
15.
KouskouraT, FragouN, AlexiouM, JohnN, SommerL, GrafD, KatsarosC, MitsiadisTA. 2011. The genetic basis of craniofacial and dental abnormalities. Schweiz Monatsschr Zahnmed. 121:636–646.
16.
LaiEH, ChangJZ, Jane YaoCC, TsaiSJ, LiuJP, ChenYJ, LinCP. 2008. Relationship between age at menarche and skeletal maturation stages in Taiwanese female orthodontic patients. J Formos Med Assoc. 107:527–532.
17.
LiQ, LiX, ZhangF, ChenF.2011. The identification of a novel locus for mandibular prognathism in the Han Chinese population. J Dent Res. 90:53–57.
18.
LuY, LiuP, ReckerRR, DengHW, DvornykV.2010. TNFRSF11A and TNFSF11 are associated with age at menarche and natural menopause in white women. Menopause. 17:1048–1054.
19.
LundstromA.1954. The importance of genetic and nongenetic factors on the facial skeleton studied in 100 pais of twins. Trans Eur Orthod Soc. 30:92–107.
20.
MagaAM, NavarroN, CunninghamML, CoxTC. 2015. Quantitative trait loci affecting the 3D skull shape and size in mouse and prioritization of candidate genes in-silico. Front Physiol. 6:92.
21.
NieminenP, MorganNV, FenwickAL, ParmanenS, VeistinenL, MikkolaML, Van Der SpekPJ, GiraudA, JuddL, ArteS, et al.2011. Inactivation of IL11 signaling causes craniosynostosis, delayed tooth eruption, and supernumerary teeth. Am J Hum Genet. 89:67–81.
22.
PallaresLF, CarbonettoP, GopalakrishnanS, ParkerCC, Ackert-BicknellCL, PalmerAA, TautzD.2015. Mapping of craniofacial traits in outbred mice identifies major developmental genes involved in shape determination. PLoS Genet. 11:e1005607.
23.
PallaresLF, HarrB, TurnerLM, TautzD.2014. Use of a natural hybrid zone for genomewide association mapping of craniofacial traits in the house mouse. Mol Ecol. 23:5756–5770.
24.
PanR, LiuYZ, DengHW, DvornykV.2012. Association analyses suggest the effects of RANK and RANKL on age at menarche in Chinese women. Climacteric. 15:75–81.
25.
RoshandelD, HollidayKL, PyeSR, WardKA, BoonenS, VanderschuerenD, BorghsH, HuhtaniemiIT, AdamsJE, BartfaiG, et al.2011. Influence of polymorphisms in the RANKL/RANK/OPG signaling pathway on volumetric bone mineral density and bone geometry at the forearm in men. Calcif Tissue Int. 89:446–455.
26.
SakakuraY, TsurugaE, IrieK, HosokawaY, NakamuraH, YajimaT.2005. Immunolocalization of receptor activator of nuclear factor-kappaB ligand (RANKL) and osteoprotegerin (OPG) in Meckel's cartilage compared with developing endochondral bones in mice. J Anat. 207:325–337.
27.
SaundersSR, PopovichF, ThompsonGW. 1980. A family study of craniofacial dimensions in the Burlington growth centre sample. Am J Orthod. 78:394–403.
28.
Tassopoulou-FishellM, DeeleyK, HarveyEM, ScioteJ, VieiraAR. 2012. Genetic variation in myosin 1H contributes to mandibular prognathism. Am J Orthod Dentofacial Orthop. 141:51–59.
29.
TomoyasuY, YamaguchiT, TajimaA, NakajimaT, InoueI, MakiK.2009. Further evidence for an association between mandibular height and the growth hormone receptor gene in a Japanese population. Am J Orthod Dentofacial Orthop. 136:536–541.
30.
WatnickSS. 1972. Inheritance of craniofacial morphology. Angle Orthod. 42:339–351.
YamaguchiT, MakiK, ShibasakiY.2001. Growth hormone receptor gene variant and mandibular height in the normal Japanese population. Am J Orthod Dentofacial Orthop. 119:650–653.
33.
ZebrickB, TeeramongkolgulT, NicotR, HortonMJ, RaoulG, FerriJ, VieiraAR, ScioteJJ. 2014. ACTN3 r577x genotypes associate with class II and deepbite malocclusions. Am J Orthod Dentofacial Orthop. 146:603–611.
34.
ZhangX, DowdDR, MooreMC, KranenburgTA, Meester-SmoorMA, ZwarthoffEC, MacdonaldPN. 2009. Meningioma 1 is required for appropriate osteoblast proliferation, motility, differentiation, and function. J Biol Chem. 284:18174–18183.
35.
ZhaoHY, LiuJM, NingG, ZhaoYJ, ZhangLZ, SunLH, XuMY, UitterlindenAG, ChenJL. 2005. The influence of Lys3Asn polymorphism in the osteoprotegerin gene on bone mineral density in Chinese postmenopausal women. Osteoporos Int. 16:1519–1524.
