Paddenberg-Schubert Eva, Küchler Erika, Bitencourt Reis Caio Luiz, Silva-Sousa Alice Corrêa, Kirschneck Christian
Department of Orthodontics, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053, Regensburg, Germany.
Department of Orthodontics, University Hospital Bonn, Medical Faculty, Bonn, Germany.
J Orofac Orthop. 2024 Jan 31. doi: 10.1007/s00056-023-00512-z.
Mandibular retrognathism (MR) is a common skeletal malocclusion in humans with a strong genetic component. Single nucleotide polymorphisms (SNPs) in genes encoding epidermal growth factor (EGF) and EGF receptor (EGFR) could be involved in the etiology of mandibular retrognathism. Therefore, in this study, we investigated whether SNPs in the genes encoding for EGF and EGFR are associated with MR in German teenagers.
This nested case-control study evaluated German orthodontic patients, aged 10-18 years. DNA, which was isolated from buccal epithelial cells using two cytobrushes, was used for genotyping analysis and digital pretreatment lateral cephalograms were examined to calculate SNB and ANB. Patients with a retrognathic mandible (SNB < 78°) were included as cases, while patients with an orthognathic mandible (SNB = 78-82°) were included as controls. Four SNPs in the genes encoding for EGF and EGFR were chosen and genotyped using real-time PCR. Allele, genotype, and haplotype frequency were compared across groups (α = 5%).
Finally, 119 patients were included in this study (45 orthognathic mandible, 74 retrognathic mandible). The minor allele G in rs4444903 (EGF) was statistically more frequent in individuals with an orthognathic mandible (p = 0.008). The haplotype formed by the mutant alleles for rs4444903|rs2237051 (EGF; G|A) was statistically more frequent in the orthognathic mandible group (p = 0.007). The SNPs rs4444903 and rs2237051 in EGF, and rs2227983 in EGFR were statistically associated with a decreasing risk of developing a retrognathic mandible according to univariate and multivariate statistical analysis (p < 0.05).
SNPs in EGF (rs4444903 and rs2237051) and EGFR (rs2227983) were associated with MR in our German sample and could be genetic biomarkers for early and individualized diagnostic identification of retrognathic mandibular development by means of genetic screening tests.
下颌后缩（MR）是人类常见的骨骼错牙合畸形，具有很强的遗传成分。编码表皮生长因子（EGF）和EGF受体（EGFR）的基因中的单核苷酸多态性（SNP）可能与下颌后缩的病因有关。因此，在本研究中，我们调查了编码EGF和EGFR的基因中的SNP是否与德国青少年的下颌后缩有关。
这项巢式病例对照研究评估了10至18岁的德国正畸患者。使用两把细胞刷从颊上皮细胞中分离出的DNA用于基因分型分析，并检查数字化预处理的头颅侧位片以计算SNB和ANB。下颌后缩（SNB＜78°）的患者作为病例纳入，而下颌正常（SNB = 78 - 82°）的患者作为对照纳入。选择编码EGF和EGFR的基因中的四个SNP，并使用实时PCR进行基因分型。比较各组的等位基因、基因型和单倍型频率（α = 5%）。
最后，本研究共纳入119例患者（45例下颌正常，74例下颌后缩）。rs4444903（EGF）中的次要等位基因G在下颌正常个体中在统计学上更为常见（p = 0.008）。由rs4444903|rs2237051（EGF；G|A）的突变等位基因形成的单倍型在下颌正常组中在统计学上更为常见（p = 0.007）。根据单变量和多变量统计分析（p＜0.05），EGF中的SNP rs4444903和rs2237051以及EGFR中的rs2227983与下颌后缩发生风险降低在统计学上相关。
在我们的德国样本中，EGF（rs4444903和rs2237051）和EGFR（rs2227983）中的SNP与下颌后缩有关，并且可以作为通过基因筛查测试对下颌后缩发育进行早期和个体化诊断识别的遗传生物标志物。
