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IRGM 基因座的单倍型变异和 rs11747270 与慢性牙周炎的易感性相关。

A haplotypic variant at the IRGM locus and rs11747270 are related to the susceptibility for chronic periodontitis.

机构信息

Department of Conservative Dentistry and Periodontology, University Hospital, Ludwig-Maximilians-University, Goethestr. 70, 80336, Munich, Germany.

出版信息

Inflamm Res. 2018 Feb;67(2):129-138. doi: 10.1007/s00011-017-1101-z. Epub 2017 Oct 5.

Abstract

OBJECTIVE AND DESIGN

Immunity-regulated GTPase M (IRGM) plays a critical role in the defense against intracellular bacteria by regulating autophagy formation. This direct genetic association study aimed to determine whether variants at the IRGM genetic locus are associated with chronic periodontitis.

MATERIALS AND SUBJECTS

Using PCR and melting curve analysis 390 periodontitis patients and 770 healthy controls have been genotyped regarding six polymorphisms in the IRGM gene (rs13361189, rs10065172, rs4958847, rs1000113, rs11747270, rs931058).

RESULTS

Frequency distribution of alleles and genotypes for the six polymorphisms were not significantly different between the periodontitis and the control group. Also following stratification according to gender and smoking no significant linkage was found for any of the IRGM variants with periodontitis. Analysis of a subsample of patients revealed a significant association for rs11747270 with severe periodontitis (p = 0.003). Pairwise linkage analysis revealed one block composed of rs13361189, rs10065172, rs4958847, rs1000113 and 11747270 with strong or even complete linkage disequilibrium (r  > 0.9). Four haplotypes showed a frequency of > 1%, among which the haplotype C-T-A-T-G was significantly associated with chronic periodontitis (p = 0.0051; OR 4.66, 95% CI 1.41-15.42).

CONCLUSIONS

One rare haplotype of the IRGM locus is significantly associated with chronic periodontitis in a German cohort.

摘要

目的和设计

免疫调节鸟苷三磷酸酶 M(IRGM)通过调节自噬形成,在抵抗细胞内细菌中发挥关键作用。本直接遗传关联研究旨在确定 IRGM 基因座的变体是否与慢性牙周炎相关。

材料和受试者

使用 PCR 和熔解曲线分析,对 390 名牙周炎患者和 770 名健康对照者的 IRGM 基因中的 6 个多态性(rs13361189、rs10065172、rs4958847、rs1000113、rs11747270、rs931058)进行了基因分型。

结果

在牙周炎组和对照组之间,六个多态性的等位基因和基因型的频率分布没有显著差异。此外,根据性别和吸烟情况进行分层后,也没有发现任何 IRGM 变体与牙周炎有显著的连锁关系。对患者亚样本的分析显示,rs11747270 与重度牙周炎显著相关(p=0.003)。成对连锁分析显示,由 rs13361189、rs10065172、rs4958847、rs1000113 和 11747270 组成的一个块具有强甚至完全连锁不平衡(r>0.9)。四个单倍型的频率>1%,其中单倍型 C-T-A-T-G 与慢性牙周炎显著相关(p=0.0051;OR 4.66,95% CI 1.41-15.42)。

结论

在德国队列中,IRGM 基因座的一个罕见单倍型与慢性牙周炎显著相关。

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