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

2004 Fiscal Year Final Research Report Summary

• Project/Area Number: 15592164
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Orthodontic/Pediatric dentistry
• Research Institution: Hiroshima University
• Principal Investigator: OKADA Mitsugi Hiroshima University, Hospital, Assistant professor, 病院, 講師 (10233347)
• Co-Investigator(Kenkyū-buntansha): SUZUKI Junji Hiroshima University, Graduate School of Biomedical Science, Associate professor, 大学院・医歯薬学総合研究科, 助教授 (90263714) ; HAYASHI Fumiko Hiroshima University, Graduate School of Biomedical Science, Research associate, 大学院・医歯薬学総合研究科, 助手 (50325180)
• Project Period (FY): 2003 – 2004
• Keywords: Prepubertal periodontitis / Leukocyte chemotaxis / fMLP receptor / Human genome / SNPs

Research Abstract

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.
Results
1.chemotactic function
The 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 receptor
The 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 receptor
We 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.