Functional polymorphisms of the FPR1 gene and aggressive periodontitis in Japanese
Functional polymorphisms of the FPR1 gene and aggressive periodontitis in Japanese
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DOI：
10.1016/j.bbrc.2007.09.105
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发表时间：
2007-12-07
影响因子：
3.1
通讯作者：
Ishikawa, Isao
中科院分区：
文献类型：
--
作者：
Gunji, Tomohiko;Onouchi, Yoshihiro;Ishikawa, Isao
侵袭性牙周炎（AgP），严重和早发型牙周炎，被认为是受显著的遗传背景影响。甲酰基肽受体1 （FPR1）是与AgP密切相关的基因。为了确定该基因的变异是否与AgP相关，我们对49名AgP患者和373名对照者进行了关联研究，使用了通过测序21.1 kb基因区域确定的30个变异。5个多态性（-12915C > T、-10056T > C、-8430A > G、301G > C和546C > A）与AgP显著相关。携带-12915T等位基因的人的多态核中性粒细胞表达的FPR1转录本水平明显低于携带-12915C等位基因的人。此外，在荧光素酶实验中，-12915T等位基因降低了转录调控活性。单倍型关联分析显示，三个snp （-12915C > T、301G > C和546C > A）在AgP患者中显著存在一个单倍型（-12915T-301G-546C） （p = 0.000020）。因此，FPR1功能的改变可能会增加AgP的风险。(C) 2007爱思唯尔公司版权所有。
Aggressive periodontitis (AgP), a severe and early onset type of periodontitis, is thought to be subject to significant genetic background effects. Formyl peptide receptor 1 (FPR1) is a gene strongly implicated in AgP. To determine whether variations in this gene are associated with AgP, we performed an association study with 49 AgP patients and 373 controls using 30 variations identified by sequencing the 21.1-kb gene region. Five polymorphisms (-12915C > T, -10056T > C, -8430A > G, 301G > C, and 546C > A) showed significant association with AgP. Polymorphonuclear neutrophils from subjects carrying the -12915T allele expressed significantly lower levels of FPR1 transcripts than those homozygous for the -12915C allele. Furthermore, the -12915T allele decreased activity of transcriptional regulation in a luciferase assay. Haplotype association analysis with three SNPs (-12915C > T, 301G > C, and 546C > A) revealed that one haplotype (-12915T-301G-546C) was significantly represented in AgP patients (p = 0.000020). Thus, altered FPR1 function might confer increased risk to AgP. (C) 2007 Elsevier Inc. All rights reserved.