IADR Abstract Archives
Genetic-Variations in Insulin-Like-Growth-Factor-1 and Growth-Hormone-Receptor Associate With Posterior-Vertical-Skull-Height During Pubertal-Growth
Objectives: Understanding how genetic variations and gene:gene interactions impact facial growth during puberty could help improve growth predictions for orthodontic and surgery treatment (Tx). This study sought to determine whether variations with the Insulin-Like-Growth-Factor-1 (IGF1) and Growth-Hormone-Receptor (GHR) genes were associated with annualized posterior vertical skull height (PVSH).
Methods: Ethics oversight was provided by Indiana University and the University of Kentucky. Initial Tx radiographs from 418 Phase II orthodontic patients were independently reviewed by 3 orthodontists for cervical vertebral maturation stage (CVMS). A subject’s maturation stage was assigned when at least 2 of 3 reviewers concurred. Subjects in CVMS3 at the start of Tx were studied further. A single examiner conducted cephalometrics on all subjects (98♀ / 84♂) using Dolphin software. Annualized growth was calculated as: (the change in growth at S-Go or Ar-Go during Tx) / (years in Tx). Subject DNA was genotyped for variations in IGF1 (rs10735380, rs1520220 and rs2946834) and GHR (rs2972408, rs4130114, rs6180). A comprehensive stepwise multiple regression identified associations between each genotypic variant and the annualized growth at S-Go or Ar-Go. A Benjamini-Hochberg adjustment was applied for multiple testing.
Results: All data for S-Go and Ar-Go were normally distributed. At the start of Tx, no significant differences were noted in the initial S-Go (or Ar-Go) measures by genotype with one exception; initial S-Go measures were larger in IGF1 rs1520220-GG males. At the end of Tx, female subjects who inherited the IGF1 rs1073580-GG genotype had significantly more annualized growth at S-Go compared to individuals who inherited the AA- or GA-genotypes. Gene:gene interactions were observed for annualized growth at S-Go in subjects who inherited specific IGF1 rs10735380*GHR rs4130114 genotype combinations. Gene:gene interactions were also observed for annualized growth at S-Go for males with specific IGF1 rs1520220*GHR rs4130114 combinations, and for annualized growth of all subjects at Ar-Go with IGF1 rs10735380*GHR rs4130114 combinations.
Conclusions: Genetic variation and gene:gene interactions associated with the IGF1 and GHR genes influence PSVH during the pubertal growth spurt in orthodontic patients starting Tx in CVMS3.
Methods: Ethics oversight was provided by Indiana University and the University of Kentucky. Initial Tx radiographs from 418 Phase II orthodontic patients were independently reviewed by 3 orthodontists for cervical vertebral maturation stage (CVMS). A subject’s maturation stage was assigned when at least 2 of 3 reviewers concurred. Subjects in CVMS3 at the start of Tx were studied further. A single examiner conducted cephalometrics on all subjects (98♀ / 84♂) using Dolphin software. Annualized growth was calculated as: (the change in growth at S-Go or Ar-Go during Tx) / (years in Tx). Subject DNA was genotyped for variations in IGF1 (rs10735380, rs1520220 and rs2946834) and GHR (rs2972408, rs4130114, rs6180). A comprehensive stepwise multiple regression identified associations between each genotypic variant and the annualized growth at S-Go or Ar-Go. A Benjamini-Hochberg adjustment was applied for multiple testing.
Results: All data for S-Go and Ar-Go were normally distributed. At the start of Tx, no significant differences were noted in the initial S-Go (or Ar-Go) measures by genotype with one exception; initial S-Go measures were larger in IGF1 rs1520220-GG males. At the end of Tx, female subjects who inherited the IGF1 rs1073580-GG genotype had significantly more annualized growth at S-Go compared to individuals who inherited the AA- or GA-genotypes. Gene:gene interactions were observed for annualized growth at S-Go in subjects who inherited specific IGF1 rs10735380*GHR rs4130114 genotype combinations. Gene:gene interactions were also observed for annualized growth at S-Go for males with specific IGF1 rs1520220*GHR rs4130114 combinations, and for annualized growth of all subjects at Ar-Go with IGF1 rs10735380*GHR rs4130114 combinations.
Conclusions: Genetic variation and gene:gene interactions associated with the IGF1 and GHR genes influence PSVH during the pubertal growth spurt in orthodontic patients starting Tx in CVMS3.
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