Association of the growth hormone receptor gene polymorphisms with mandibular height in a Korean population

Growth hormone receptor gene (GHR) is one of the likely candidates for determining morphological traits, because GH is a key regulator of bone growth. The genetic association of GHR in exon 10 with mandibular ramus height has been found in different populations, Japanese and Chinese. On the other hand, two common isoforms of GHR, one full-length (fl-GHR) and the other lacking the extracellular domain encoded by exon 3 (d3-GHR), are associated with differences in responsiveness to GH. The purpose of this study involving 159 Korean subjects was to study the associations between a GHR polymorphism (d3/fl-GHR) that results in genomic deletion of exon 3 and craniofacial morphology, and to study the associations between GHR genotypes in exon 10 and craniofacial morphology. Moreover, the allelic frequencies in a multi-ethnic population (24 Han Chinese, 24 African-Americans, 24 European-Americans, and 24 Hispanics) in a GHR polymorphism (d3/fl-GHR) were compared in this study. The five craniofacial linear measurements (cranial base length, maxillary length, overall mandibular length, mandibular corpus length, and mandibular ramus height) obtained from lateral cephalograms were examined as craniofacial morphology. We found that the d3/fl-GHR polymorphism had no association for any measurements, and a statistically significant association (P = 0.024) between the GHR polymorphisms P561T and C422F in exon 10 and mandibular ramus height. Neither SNPs besides P561T and C422F polymorphisms in exon 10 nor the measurements besides mandibular ramus height have statistically significances. Both derived alleles at P561T and C422F SNPs were highly associated with only one haplotype, haplotype-4 in Korean population. As quantitative haplotype association, the results showed a significant difference in mandibular ramus height between individuals having one haplotype-4 and others without haplotype-4 (P = 0.028). Moreover, we found that the d3/fl-GHR polymorphism showed diverse frequency in different population. Regarding GHR genotypes in exon 10, the present study mostly reflected the results obtained for a Japanese population, although our current study does not replicate the correlation between the I526L polymorphism of GHR and mandibular ramus height as was reported in a previous study of Han Chinese. The results of the present study suggest that the GHR exon 10 SNPs, not d3/fl-GHR, contribute to changes in the mandibular ramus height of Koreans.     

Effects of growth hormone and ultrasound on mandibular growth in rats: MicroCT and toxicity analyses

It has been shown by previous studies that mandibular growth can be enhanced by the systemic administration of recombinant growth hormone (rGH) and/or local application of therapeutic low intensity pulsed ultrasound (LIPUS). The purpose of this study was to determine if local injection of rGH and application of LIPUS to the temporomandibular joint (TMJ) would synergistically enhance mandibular growth. In an animal study, the effect of rGH, LIPUS, and combination of rGH and LIPUS on male Sprague–Dawley rats was observed. Mandibular growth was evaluated by measuring total hemimandibular and condylar bone volume and bone surface area as well as condylar bone mineral density (BMD) after 21 days on dissected rats’ mandibles using micro-computed tomography (MicroCT). The expression of c-jun mRNA extracted from the liver of each of these rats was also quantified by real-time polymerase chain reaction to evaluate possible systemic effect of local rGH administration. Significant growth stimulation was observed in the mandibular and condylar bone of the animals treated with rGH, LIPUS, and rGH/LIPUS combined when compared with the control group. Bone volume, surface area, condylar bone mineral density, and c-jun expression were also compared between the treatment groups and the control in the liver. The results suggest that mandibular growth may be enhanced by injection of rGH or LIPUS application. The current study although showed synergetic effect of rGH and LIPUS application in increasing mandibular condylar head length, there was no significant changes in mandibular bone volume using both treatments together when compared to the two individual treatments. Moreover, combined rGH and LIPUS decreased condylar bone mineral density than each treatment separately. Future research could be directed to investigate the effects of different rGH doses and/or different LIPUS exposures parameters on lower jaw growth.     

Three-dimensional analysis of molar compensation in patients with facial asymmetry and mandibular prognathism

Objective:To evaluate the characteristic transverse dental compensations in patients with facial asymmetry and mandibular prognathism and to compare features of dental compensations between two types of mandibular asymmetry using 3-dimensional (3D) cone-beam computed tomography (CBCT).Materials and Methods:Seventy-eight adult patients with skeletal Class I (control group; n  =  33; 19 men and 14 women) or skeletal Class III with facial asymmetry (experimental group; n  =  45; 23 men and 22 women) were included. The experimental group was subdivided into two groups according to the type of mandibular asymmetry: translation type (T-type; n  =  20) and roll type (R-type; n  =  19). CBCT images were acquired before orthodontic treatment and 3D analyses were performed.Results:The transverse dental distance was significantly different between the two groups only at the palatal root apex of the maxillary first molar (P < .05). In the experimental group, the first molar axes were compensated significantly on both arches except the maxillary nondeviated side. The vertical molar heights were different between the two groups only on the maxillary arch (P < .001). The R-type showed greater mandibular ramal length difference and menton deviation than the T-type (P < .001). In the R-type, transverse compensation of the maxillary first molars was more obvious than with the T-type, which resulted in canting in the maxillary occlusal plane.Conclusions:Mandibular asymmetry with prognathism showed a characteristic transverse dental compensation pattern. The mandibular asymmetry type influenced the amount and direction of molar compensation on the maxillary arch.     

The main occluding area in normal occlusion and mandibular prognathism

Objective:To clarify whether the concept of main occluding area, where hard food is initially crushed, exists in patients who have a jaw deformity.Materials and Methods:Nineteen subjects with normal occlusion, 18 patients with mandibular prognathism, and 11 patients with mandibular prognathism who had undergone orthognathic surgery participated in this study. The main occluding area was identified by clenching Temporary Stopping. The coincidence, location of the main occluding area, and distance from the first molars to main occluding area were examined.Results:High coincidence of the main occluding area was obtained in all groups, signifying that the main occluding area exists even in these patients. Mandibular main occluding area was located on the first molar in all groups. Maxillary main occluding area in subjects with normal occlusion was located on the first molar. However, it was located on the second premolar and first molar in patients with mandibular prognathism, and on the first and second molars in patients with mandibular prognathism who had undergone orthognathic surgery. There was a statistically significant difference in distance from the maxillary first molar to the main occluding area among groups, but there was no difference in the distance from the mandibular first molar among groups.Conclusion:The main occluding area is more stable on the mandibular first molar than the maxilla in all groups.     

Influence of growth hormone on the mandibular condylar cartilage of rats

Growth hormone (GH) stimulates mandibular growth but its effect on the mandibular condylar cartilage is not well understood. OBJECTIVE: This study was designed to understand the influence of GH on mitotic activity and on chondrocytes maturation. The effect of GH on cartilage thickness was also determined. DESIGN: An animal model witt differences in GH status was determined by comparing mutant Lewis dwarf rats with reduced pituitary GH synthesis (dwarf), with normal rats and dwarf animals treated with GH. Six dwarf rats were injected with GH for 6 days, while other six normal rats and six dwarf rats composed other two groups. Mandibular condylar tissues were processed and stained for Herovici's stain and immunohistochemistry for proliferating cell nuclear antigen (PCNA) and alkaline phosphatase (ALP). Measurements of cartilage thickness as well as the numbers of immunopositive cells for each antibody were analysed by one-way analysis of variance. RESULTS: Cartilage thickness was significantly reduced in the dwarf animals treated with GH. PCNA expression was significant lower in the dwarf rats, but significantly increased when these animals were treated with GH. ALP expression was significant higher in the dwarf animals, while it was significantly reduced in the dwarf animals treated with GH. CONCLUSIONS: The results from this study showed that GH stimulates mitotic activity and delays cartilage cells maturation in the mandibular condyle. This effect at the cellular level may produce changes in the cartilage thickness.     

Identification of SNP markers on 1p36 and association analysis of EPB41 with mandibular prognathism in a Chinese population

Objective

The results of a genome-wide scan suggested that chromosome locus 1p36 might be linked to the etiology of mandibular prognathism (MP) amongst Asian ethnicities. In this study, we performed a two-stage case-control association study to determine whether one or more genes that confer susceptibility to MP are located within this genomic region.

Design

In the first stage of the study, we examined 103 single nucleotide polymorphisms (SNPs) on 1p36 across an 8.6 Mb critical region and within four candidate genes in 158 cases and 147 controls to identify genes associated with MP. In the second stage of the study, we examined an additional 23 SNPs within the erythrocyte membrane protein band 4.1 (EPB41) gene in 211 cases and 224 controls.

Results

Four SNPs located in the EPB41 gene showed possible allelic and genotypic associations with MP (P < 0.03 and P < 0.05, respectively) in the first stage. In the analysis of single SNPs in the second stage, the allele of rs4654388 showed the strongest significant association with MP (P = 0.008) and the rs4654388 G-allele was associated with a significantly increased risk of MP (OR: 1.78, 95% CI: 1.16-2.74). Haplotype analysis revealed that MP was associated significantly with haplotype GTTCAGGT (P_corrected = 0.031), which included the rs4654388 G-allele.

Conclusions

An association between genetic polymorphisms in the EPB41 gene and MP has been observed. Although the polymorphisms which may contribute to MP have not been determined, the results of our study suggest that the EPB41 gene could confer susceptibility to MP.     

106 名中国汉族人生长激素受体基因单核苷酸多态性分析

目的　研究中国汉族人群生长激素受体 (GHR)基因的单核苷酸多态性 (SNP) ,观察这些SNP在汉族人群中的分布。方法　应用 370 0型自动测序仪对 10 6名中国汉族非亲缘关系人的GHR基因部分外显子进行序列测定 ,确定其单核苷酸多态位点及基因型。结果　在外显子 6、10上共有 6个SNP位点 ,5个集中于第 10外显子 ,各等位基因频率与美国国立生物技术信息中心 (NCBI)报道均有差别 ,位于 16 30A >C (I5 2 6L)处的单核苷酸多态性杂合度最高 ,为 4 7 6 %。其中 14 83A>C (P4 77T)、1735A >C(P5 6 1T)、1319G >T (C4 2 2F)均有极性改变。美国国立生物技术信息中心报告的外显子 6的 5 36A >G未在本项研究人群中检测到。结论　生长激素受体基因SNP呈不均匀分布且具有种族差异性     

Effects of growth hormone and functional appliance on mandibular growth in an adolescent rat model

Objectives:To investigate the individual and synergistic effects of growth hormone (GH) and functional appliance (FA) on mandibular growth in an adolescent rat model.Materials and Methods:Forty adolescent (6-week-old) female Wistar rats were randomly divided into four groups (10 rats in each group). The control group received a sham treatment (intra-abdominal injection of phosphate-buffered saline), the GH group received an intra-abdominal injection of recombinant human growth hormone, the FA group was treated with a mandibular advancement device, and the GH+FA group received both the GH and FA treatments. The amount of mandibular growth in each group was measured quantitatively using cone-bean computed tomography. The growth of condylar cartilage and expression of matrix metalloproteinases–1 and –13 (MMP-1 and MMP-13) and type II and X collagen (Col II and Col X) were assessed using histological staining and immunostaining techniques.Results:After 4 weeks, there was significant mandibular growth in the FA group compared with the control group (P < .05). The GH+FA group had significantly greater mandibular length, thickness of condylar cartilage, and expression of MMP-1, MMP-13, Col II, and Col X in the cartilage than the other groups (P < .05). The GH+FA group and GH group had significantly greater weight than the FA and control groups (P < .05).Conclusions:The FA as well as GH+FA stimulated mandibular growth in adolescent rats.     

Lack of association between chronic periodontitis and the Toll-like receptor 4 gene polymorphisms in a Czech population

BACKGROUND AND OBJECTIVE: Periodontitis is a bacterially induced chronic inflammatory disease and a major cause of tooth loss among adults. Toll-like receptors are signal molecules essential for the cellular response to bacterial cell wall components. The aim of this study was to investigate relationships between chronic periodontitis and variations in the TLR4 gene. MATERIAL AND METHODS: A total of 171 patients with chronic periodontitis and 218 unrelated controls were genotyped for the Asp299Gly (896A>G) and Thr399Ile (1196C>T) polymorphisms of the TLR4 gene. RESULTS: Both variants were in nearly complete linkage disequilibrium. No homozygotes for the less common alleles, 299Gly and 399Thr, respectively, were found. The prevalence of the Asp299Gly and the Thr399Ile heterozygotes was 5.3% and 5.0% in controls, and 7.0% and 7.0% in periodontitis patients. CONCLUSION: In conclusion, TLR4 gene polymorphisms were not significantly associated with the susceptibility to, or severity of, chronic periodontitis in our population.     

IL-1B＋3954C/T和IL-1B-511C/T基因多态性和种植体周围炎的相关性研究

目的：探讨研究种白介素1（IL-1）基因＋3954和-511位点单核酸多态性和种植体周围炎的关系以及临床意义。方法：采用病例对照实验设计,选取种植体炎患者以及对照组各50名,应用聚合酶链反应—限制性内切酶片段长度多态性基因分析方法研究两组IL-1B基因＋3954位点和-511位点基因型和等位基因分布特点,并探讨其与种植体周围炎的相关性。结果：IL-1B基因＋3954位点CC、CT基因型检出率为93%和7%,无TT基因型,两种基因型和C、T等位基因频率在组间分布差异无统计学意义（P〉0.05）;IL-1B基因-511位点主要以CT为主,检出率为58%,CC、CT基因型检出率都为21%。结论：排除吸烟,牙周炎病史等影响因素后,IL-1B基因＋3954位点和-511位点的多态性与种植体周围炎炎的易感性无关。     

Growth hormone receptor gene is related to root length and tooth length in human teeth

Objectives:To examine the relationship between tooth length and growth hormone receptor (GHR) gene variants in a healthy Japanese population.Materials and Methods:The subjects consisted of 193 Japanese adults (69 men, 124 women), aged 13 to 56 years. Genomic DNA was extracted from saliva and genotyped GHR rs6184 and rs6180 variants using the Taqman genotyping. Computed tomography (CT) images were acquired using a dental cone-beam CT scanner and reconstructed using open-source OsiriX medical image processing software. The maxillary (upper; U) and mandibular (lower, L) central incisors (1), lateral incisors (2), canines (3), first premolars (4), second premolars (5), first molars (6), and second premolars (7) were evaluated. Teeth were assessed for crown height (CH), root length (RL), overall tooth length (C+R), and crown to root ratio (C/R). The relationships between GHR variants and CH, RL, C+R, and C/R were statistically examined.Results:The GHR variant rs6184 was associated with the root lengths and tooth length for the upper and lower lateral incisors and upper canines (U2 RL; U3 RL, C+R; L2 RL [P < .05]).Conclusions:The results indicate that the GHR rs6184 variant is associated with tooth length and ratio dimensions in a Japanese cohort. Further studies utilizing a larger sample size are needed to confirm this finding.     

微RNA在下颌髁突软骨生长发育中作用的研究进展

微RNA(micro RNA,miRNA)是一类小的非编码单链RNA,通过与信使RNA结合发挥其生物学作用。研究显示miRNA可能在调节下颌髁突软骨的生长发育中起重要作用。本文就miRNA的产生及其作用机制,对下颌髁突软骨生长发育相关的miRNA研究进展进行综述,以期助于进一步研究下颌髁突软骨生长发育。     

牙周炎患者TLR2,TLR4基因多态性研究

目的：研究TLR2、TLR4基因多态性分布,探讨其与牙周炎的发病和严重程度之间的相关性。方法：选择40位侵袭性牙周炎（AgP）患者及50名慢性牙周炎（CP）患者为实验对象,以100名牙周健康者作为对照组。从全血样本中提取基因组DNA,采用PCR-RFLP方法进行TLR2、TLR4基因多态性分析,使用凝胶电泳和溴乙锭检测等位基因。结果：正常对照组和（AgP）、（CP）患者均为TLR2 Arg677Trp基因的杂合型。在A妒组与CP组患者中未发现TLR2 Arg753Gln的突变型,而对照组中该基因频率为6％。在所有研究对象中都未发现TLR4 Asp299Gly和Thr399Ile的基因多态性。结论：TLR2、TLR4基因的多态性与牙周炎之间无相关性。     

Relationship between vitamin D receptor gene polymorphism and periodontitis

Recent studies have shown that vitamin D receptor (VDR) gene polymorphism had regulatory effects on bone mineral density (BMD) and bone turnover. The VDR gene has also been indicated as a candidate gene for the susceptibility of osteoporosis. However, it is unclear whether VDR genotypes could be associated with alveolar bone loss of patients with periodontitis, or whether vitamin D receptor gene could be a candidate gene for susceptibility to periodontitis. The purpose of this study was to answer these two questions. METHODS: Twenty-four cases of adult periodontitis (AP), 37 cases of early onset periodontitis (EOP) and 39 healthy controls were recruited for the study. Individual samples of venous blood and DNA were obtained from each subject. Genotypes of the TaqI VDR gene were determined by PCR and TaqI restriction endonuclease digestion. RESULTS: One out of 24 AP patients, nine out of 37 EOP patients and two out of 39 healthy controls were detected with Tt genotype, while the rest had the TT genotype. The detected frequency of Tt genotype was significantly higher in EOP patients (24.3%) than in AP patients (4.2%) and healthy controls (5.1%). The frequency of t allele was also significantly higher in EOP patients. There was no statistical difference in the distribution of TaqI VDR genotypes between AP patients and healthy controls. The study suggests that Tt genotype might be a risk indicator for the susceptibility to EOP. Carriage of the allele (t) of the TaqI VDR gene may increase the risk of developing EOP.     

Speed of sound measurements in mandibular and phalangeal bone during growth

The micromechanical and elastic properties of bone, its structural maturity and, indirectly, mineral density are important factors for the planning and assessment of orthodontic and/or jaw orthopaedic treatment. This clinical study was undertaken to evaluate age-related changes in the anterior mandibular body. The speed of sound (SOS) has demonstrated age dependency in various peripheral bones and has been proposed as an alternative method for investigating bone parameters without the use of radiation. The ultrasound transmission velocity was measured in 184 healthy subjects (93 females, 91 males; mean age 17.6±13.7 years). According to the statistical analysis, the data did not reveal any gender- related differences, but were significantly age-dependent. Different kinetics were established between the maturity of the phalanx and the anterior mandible. Further clinical investigations of age-dependent structural changes in bone maturation parameters may provide information that should be taken into account for early functional jaw orthopaedic treatment. Received: 31 January 2000 / Accepted: 15 May 2000     

Association of vitamin D receptor gene polymorphisms in Chinese patients with generalized aggressive periodontitis

Background and Objective:  The clinical features suggest that genetic factors may have a strong influence on susceptibility to aggressive periodontitis. The aim of this study was to investigate the association of vitamin D receptor gene polymorphisms with generalized aggressive periodontitis in Chinese patients.
Material and Methods:  A restriction fragment length polymorphism (RFLP) for 10,438,141 C to T (rs1544410, Bsm I), 10,382,063 A to G (rs731236, Taq I), 10,382,143 C to A (rs7975232, Apa I) and 10,416,201 A to G (rs2228570, Fok I) of vitamin D receptor gene was analysed by polymerase chain reaction, followed by digestion with restriction enzymes and gel electrophoresis. The genotypes of 51 generalized aggressive periodontitis patients and 53 periodontally healthy control subjects were analysed. The genotypic and allelic frequencies of each polymorphism site for the patients and control subjects were compared.
Results:  The distribution of vitamin D receptor Fok I genotypes and alleles between the two groups was significantly different ( p =  0.043 and p  = 0.012, respectively). The F allele seemed to increase the susceptibility of aggressive periodontitis (odds ratio = 2.02, 95% confidence interval = 1.16–3.50) in Chinese patients. There was no significant difference in the genotype distribution or the allele frequencies of vitamin D receptor Bsm I, Apa I and Taq I between two groups.
Conclusion:  The study indicates that Fok I polymorphism of vitamin D receptor gene might be associated with generalized aggressive periodontitis in Chinese patients. In addition, the carriage of F allele increases the risk of developing generalized aggressive periodontitis.     

Association of vitamin D receptor gene polymorphisms with chronic and aggressive periodontitis in Jordanian patients

Vitamin D acts through binding with vitamin D receptor (VDR) and is responsible for regulating bone metabolism and mineralization; it also suppresses the immune system. The aim of this study was to investigate if VDR gene polymorphisms are associated with chronic periodontitis (CP) and aggressive periodontitis (AgP) in a Jordanian population. A total of 99 patients with CP, 63 patients with AgP, and 126 controls were genotyped using PCR‐restriction fragment length polymorphism (RFLP) for BsmI, ApaI, and TaqI single nucleotide polymorphisms (SNPs). The association was determined after correcting for confounding factors using multivariate logistic regression analysis. Estimation of haplotype frequencies was carried out using the EH program, and haplotypes were constructed using the phase 2.1 program. After correcting for confounding factors, multivariate logistic regression analysis revealed that inheritance of the BsmI bb genotype or the ApaI aa genotype was associated with increased risk of developing CP (OR = 2.4 and OR = 3.4, respectively) but with reduced risk of developing AgP (OR = 0.4 and OR = 0.3, respectively). This was further supported by association of the ba haplotype with CP but not with AgP. This study supports an association of VDR gene polymorphisms with CP and AgP in a Jordanian population; however, the pattern of association was different between the two diseases.