Formylpeptide receptor single nucleotide polymorphism 348T>C and its relationship to polymorphonuclear leukocyte chemotaxis in aggressive periodontitis.
Formylpeptide receptor single nucleotide polymorphism 348T>C and its relationship to polymorphonuclear leukocyte chemotaxis in aggressive periodontitis.
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DOI：
10.1902/jop.2009.090103
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发表时间：
2009-09
影响因子：
4.3
通讯作者：
Walters JD
中科院分区：
文献类型：
--
作者：
Maney P;Walters JD
侵袭性牙周炎（AgP）与多形核白细胞（PMN）对细菌N-甲酰肽的趋化性受损有关。甲酰肽受体（FPRs）在引导中性粒细胞到达感染部位中起主要作用。先前的工作揭示了在非裔美国人中FPR 1单核苷酸多态性（SNP）348 T>C和AgP之间的显著关联。我们检验了348 T通过降低FPR mRNA表达，从而增加对AgP的敏感性，从而损害PMN趋化性的假设。从非裔美国人受试者（37例AgP病例和38例对照）中获得血液样本。在改良的Boyden小室中测定新鲜分离的中性粒细胞对N-甲酰-Met-Leu-Phe的趋化性。从PMNs中分离RNA，并通过真实的时间PCR定量FPR 1基因表达。为了检测FPR 1 5'SNP，分离基因组DNA，并对跨越FPR 1 5'区域的四个片段进行PCR扩增和测序。分析SNP 348 T>C与5'SNP之间的单倍型关联。348 T纯合子基因型仅见于AgP组（P=0.017，OR =18.9）。与对照组和348 C/C或348 T/C基因型相比，该基因型的受试者的PMN趋化反应显著降低（P<0.05）。348 C/C、348 C/T和348 T/T基因型受试者之间的PMNFPR 1表达无显著差异。检测到11个FPR 1 5'SNP，但没有预测的单倍型反映与AgP或348 T的关联。虽然348 T/T基因型是相对罕见的，它与显着受损的中性粒细胞趋化性和发展AgP的风险增加，在非洲裔美国人。这些关联似乎与表达348 T的受试者中FPR 1转录物的显著减少无关。
Aggressive periodontitis (AgP) is associated with impaired polymorphonuclear leukocyte (PMN) chemotaxis toward bacterial N-formylpeptides. Formylpeptide receptors (FPRs) play a major role in guiding PMNs to infection sites. Previous work revealed a significant association between FPR1 single nucleotide polymorphism (SNP) 348T>C and AgP in African Americans. We tested the hypothesis that 348T impairs PMN chemotaxis by decreasing FPR mRNA expression, thereby increasing susceptibility to AgP. Blood samples were obtained from African American subjects (37 AgP cases and 38 controls). Chemotaxis to N-formyl-Met-Leu-Phe by freshly isolated PMNs was assayed in a modified Boyden chamber. RNA was isolated from PMNs and FPR1 gene expression was quantified by real time PCR. To detect FPR1 5’ SNPs, genomic DNA was isolated and four fragments spanning the FPR1 5’ region were PCR-amplified and sequenced. Haplotype associations between SNP 348T>C and 5’ SNPs were analyzed. The homozygous 348T genotype was only found in AgP cases (P=0.017, odds ratio=18.9). Subjects with this genotype exhibited a significantly lower PMN chemotactic response relative to controls and to subjects with the 348C/C or 348T/C genotypes (P<0.05). There were no significant differences in PMN FPR1 expression between subjects with the 348C/C, 348C/T and 348 T/T genotypes. Eleven FPR1 5’ SNPs were detected, but none of the predicted haplotypes reflected associations with AgP or with 348T. Although the 348T/T genotype is relatively rare, it is associated with significantly impaired PMN chemotaxis and an increased risk of developing AgP in African Americans. These associations do not appear to be related to significant reductions in FPR1 transcripts in subjects expressing 348T.
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DOI：
10.1152/ajpregu.00307.2007
发表时间：
2007-09-01
影响因子：
2.8
作者：
Bailey, Michael T.;Engler, Harald;Sheridan, John F.
通讯作者：
Sheridan, John F.
影响因子：
6.7
作者：
Nibali, L.;Parkar, M.;Griffiths, G. S.
通讯作者：
Griffiths, G. S.
影响因子：
3.5
作者：
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通讯作者：
Trembath, RC
DOI：
10.1016/j.bbrc.2007.09.105
发表时间：
2007-12-07
影响因子：
3.1
作者：
Gunji, Tomohiko;Onouchi, Yoshihiro;Ishikawa, Isao
通讯作者：
Ishikawa, Isao
缺乏N-甲基肽受体的小鼠中抗菌宿主防御受损。
影响因子：
15.3
作者：
Gao, J L;Lee, E J;Murphy, P M
通讯作者：
Murphy, P M