Analysis on SNPs of N-formyl-methionyl-leucyl-phenylalanine receptor in human genome

人类基因组N-甲酰基-甲硫氨酰-亮氨酰-苯丙氨酸受体SNPs分析

• 批准号: 15592164
• 负责人: OKADA Mitsugi
• 金额: $ 2.24万
• 依托单位: Hiroshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15592164/
• 关键词: Prepubertal periodontitis; Leukocyte chemotaxis; fMLP receptor; Human genome; SNPs; fMLP recepter

The purpose of this study was to evaluate a risk of periodontal disease by the genetic diagnosis of human leukocyte chemotactic function of subjects and family members and sequenced N-formyl-methionyl-leucyl-phenylalanine (fMLP) gene. Polymorphonuclear neutrophils (PMNs) are attracted to sites of infection by N-formyl-methionyl-leucyl-phenylalanine (fMLP) chemoattractants. The cellular functions are disrupted in PMN from prepubertal periodontitis (PP) patients.Results1.chemotactic functionThe chemotactic function in PP patients were depressed from 6.7% to 83.7% of control value. We found four immediate family members who had depressed chemotactic function in 3 gingivitis and 1 adult periodontitis cases. In addition, 9 subjects (3 gingivitis and 6 PP patients) revealed low response to chemotactic function by fMLP chemoattractants. If parents had depressed chemotactic function, either children of those was found similar functional disorder.2.Production of mRNA of fMLP receptorThe amount of mRNA of fMLP receptor increased more than 30 times than that of control subjects with and without chemoattractants. It was suggested that correct mRNA could not produced in PP patients and was found to be negative feedback in control and PP patients.3.SNPs analysis of fMLP receptorWe employed a direct sequence of subject target DNA to evaluate the SNPs analysis. Neither c.329T>C nor c.378C>G were detected in the allele sequenced. Seven SNPs were identified. The c.126G>A, c.209C>G, c.301G>C, c.546C>A, c.576T>G, c.627C>A, and c.702T>C SNPs were detected. A c.301G>C SNP was associated with the PP patient and either parent with depressed neutrophil chemotaxis.In conclusion, A c.301G>C SNP could be a risk factor for periodontitis family.

本研究的目的是通过对受试者和家庭成员的人类白细胞趋化功能进行遗传学诊断，并对N-甲酰基-甲硫氨酰-亮氨酰-苯丙氨酸（fMLP）基因进行测序，以评估牙周病的风险。多形性中性粒细胞（PMNs）被N-甲酰基-甲硫氨酰-亮氨酰-苯丙氨酸（fMLP）化学引诱物吸引到感染部位。结果：1.趋化功能：牙周炎患者外周血中性粒细胞趋化功能由正常对照组的6.7%下降到83.7%。在3例牙龈炎和1例成人牙周炎患者中，我们发现4名直系亲属的趋化功能低下。此外，9例受试者（3例牙龈炎和6例PP患者）对fMLP趋化因子的趋化功能反应较低。2. fMLP受体mRNA的产生fMLP受体mRNA的表达在有或无趋化因子的情况下，fMLP受体mRNA的表达量比对照组增加30倍以上。提示PP患者无法产生正确的mRNA，并且在对照组和PP患者中发现负反馈。3. fMLP受体的SNP分析我们采用受试者靶DNA的直接序列来评估SNP分析。在测序的等位基因中未检测到c.329T>C和c.378C>G。鉴定了7个SNP。检测到c.126G>A、c.209C>G、c.301G>C、c.546C>A、c.576T>G、c.627C>A和c.702T>C SNP。301 G>C SNP与PP患者及父母一方中性粒细胞趋化性降低相关，提示301 G>C SNP可能是牙周炎家族的危险因素。