GHR and IGF2R genes may contribute to normal variations in craniofacial dimensions: Insights from an admixed population

Author(s):Show less -

Maranon-Vasquez, Guido Artemio ^[1] ; Vieira, Alexandre R. ^[2] ; de Carvalho Ramos, Alice Gomes ^[3] ; Dantas, Beatriz ^[3] ; Romano, Fabio Lourenco ^[1] ; Palma-Dibb, Regina Guenka ^[4] ; Arid, Juliana ^[1] ; Carpio, Karla ^[1] ; Nelson-Filho, Paulo ^[1] ; de Rossi, Andiara ^[1] ; Scariot, Rafaela ^{[5, 6]} ; Levy, Simone Carvalho ^[7] ; Antunes, Livia Azeredo A. ^{[8, 7]} ; Antunes, Leonardo Santos ^{[8, 9]} ; Kuchler, Erika C. ^{[1, 10]}

Affiliation

^[1] Univ Sao Paulo, Dept Pediat Dent, Sch Dent Ribeirao Preto, USP Campus, Ave Cafe S-N, BR-14040904 Ribeirao Preto, SP - Brazil

^[2] Univ Pittsburgh, Sch Dent Med, Dept Oral Biol, 412 Salk Pavil, 335 Sutherland St, Pittsburgh, PA 15261 - USA

^[3] Amazonian Educ Inst, Manaus, Amazonas - Brazil

^[4] Univ Sao Paulo, Dept Restorat Dent, Sch Dent Ribeirao Preto, Ribeirao Preto, SP - Brazil

^[5] Univ Fed Parana, Dept Oral & Maxillofacial Surg, Curitiba, Parana - Brazil

^[6] Posit Univ, Dept Oral & Maxillofacial Surg, Curitiba, Parana - Brazil

^[7] Fluminense Fed Univ, Sch Dent, Grad Program, Niteroi, RJ - Brazil

^[8] Fluminense Fed Univ, Sch Dent, Dept Specif Format, Nova Friburgo, RJ - Brazil

^[9] Fluminense Fed Univ, Sch Dent, Clin Res Unit, Niteroi, RJ - Brazil

^[10] Posit Univ, Dept Dent, Curitiba, Parana - Brazil

• Document type: Journal article
• Source: AMERICAN JOURNAL OF ORTHODONTICS AND DENTOFACIAL ORTHOPEDICS; v. 158, n. 5, p. 722+, NOV 2020.
• Web of Science Citations: 0

Abstract

Introduction: This study aimedto determine whether single nucleotide polymorphisms in the growth hormone receptor (GHR) and insulin-like growth factor 2 receptor (IGF2R) genes are associated with different craniofacial phenotypes. Methods: A total of 596 orthodontic and 98 orthognathic patients from 4 cities in Brazil were included for analyses. Angular and linear cephalometric measurements were obtained, and phenotype characterizations were performed. Genomic DNA was collected from buccal cells and single nucleotide polymorphisms in GHR (rs2910875, rs2973015, rs1509460) and IGF2R(rs2277071, rs6909681, rs6920141) were genotyped by polymerase chain reactions using TaqMan assay. Genotype-phenotype associations were assessed in the total sample (statistical significance was set at P<8.333 x 10(-3)) and by a meta-analytic approach implemented to calculate the single effect size measurement for the different cohorts. Results: Rare homozygotes for the GHR rs2973015 showed increased measurements for the lower anterior facial height (ANS-Me) and mandibular sagittal lengths (Co-Gn and Go-Pg). In contrast, common homozygotes for the IGF2R rs6920141 presented reduced measurements for these dimensions (ANS-Me and Go-Pg). Furthermore, the less common homozygotes for IGF2R rs2277071 had reduced maxillary sagittal length (Ptm0-A0). The meta-analytical approach replicated the associations of rs2973015 with ANS-Me, rs2277071 with Ptm'-A', and rs6920141 with Go-Pg. Conclusions: Our results provide further evidence that GHR contributes to the determination of mandibular morphology. In addition, we report that IGF2R is a possible gene associated with variations in craniofacial dimensions. Applying meta-analytical approaches to genetic variation data originating from likely underpowered samples may provide additional insight regarding genotype and/or phenotype associations. (AU)

• FAPESP's process: 16/08149-1 - Evaluation of the role of estrogen in dentofacial tissues
• Grantee: Erika Calvano Kuchler
• Support Opportunities: Scholarships in Brazil - Young Researchers
• FAPESP's process: 15/06866-5 - Evaluation of the role of estrogen in dentofacial development
• Grantee: Erika Calvano Kuchler
• Support Opportunities: Research Grants - Young Investigators Grants