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细胞黏附分子基因多态性与复发性阿弗他口炎的关联

Association of cell adhesion molecule gene polymorphisms with recurrent aphthous stomatitis.

作者信息

Alkhateeb Asem, Karasneh Jumana, Abbadi Hebah, Hassan Ahmad, Thornhill Martin

机构信息

Department of Biotechnology and Genetics, Jordan University of Science and Technology (JUST), Irbid, Jordan.

出版信息

J Oral Pathol Med. 2013 Nov;42(10):741-6. doi: 10.1111/jop.12100. Epub 2013 Jun 18.

DOI:10.1111/jop.12100
PMID:23772946
Abstract

BACKGROUND

Recurrent aphthous stomatitis (RAS) is a common oral ulcerative condition. At ulcer sites vascular adhesion molecule-1 (VCAM-1), E-selectin and intercellular adhesion molecule-1 (ICAM-1) are strongly expressed on blood vessels, and ICAM-1 is expressed on keratinocytes. Expression of these molecules would promote leukocyte accumulation and invasion of the epithelium. Thus, polymorphisms in these candidate genes might contribute to RAS susceptibility. We investigated whether the inheritance of specific selectin, ICAM and VCAM gene polymorphisms is associated with RAS susceptibility.

METHODS

Ninety-six RAS cases and 153 controls were recruited from a Jordanian population. Blood was collected for hematological investigations and genotyping. Six SNPs were genotyped: E-selectin rs5361 and rs1805193, L-selectin, rs2205849, ICAM-1 rs5498, ICAM-5 rs885743 and VCAM-1 rs1800821. Association was determined using chi-square and binary logistic regression analysis after correcting for confounding factors. Linkage disequilibrium was determined using the EH program, and the Phase 2.1 program was used to construct and compare haplotypes between cases and controls.

RESULTS

There was a significant association of the A allele (Pcorr  = 0.027), AA and AC genotypes (OR = 10.9 and 9.0, respectively) of the E-selectin rs5361 gene polymorphism and TAA haplotype (rs2205849, rs5361, and rs1805193, respectively; P = 0.03) with RAS. None of the other SNPs showed a significant association.

CONCLUSIONS

This is the first report to link inheritance of the A allele, AA and AC genotypes of the E-selectin rs5361 polymorphism with increased risk of RAS. Further studies in different patient cohorts are needed to confirm the association, and functional analyses might clarify the biological significance of the association.

摘要

背景

复发性阿弗他口炎(RAS)是一种常见的口腔溃疡性疾病。在溃疡部位,血管细胞黏附分子-1(VCAM-1)、E-选择素和细胞间黏附分子-1(ICAM-1)在血管上强烈表达,而ICAM-1在角质形成细胞上表达。这些分子的表达会促进白细胞聚集和上皮细胞浸润。因此,这些候选基因的多态性可能与RAS易感性有关。我们研究了特定选择素、ICAM和VCAM基因多态性的遗传是否与RAS易感性相关。

方法

从约旦人群中招募了96例RAS患者和153名对照。采集血液进行血液学检查和基因分型。对6个单核苷酸多态性(SNP)进行基因分型:E-选择素rs5361和rs1805193、L-选择素rs2205849、ICAM-1 rs5498、ICAM-5 rs885743和VCAM-1 rs1800821。在校正混杂因素后,使用卡方检验和二元逻辑回归分析确定关联性。使用EH程序确定连锁不平衡,并使用Phase 2.1程序构建和比较病例组与对照组之间的单倍型。

结果

E-选择素rs5361基因多态性的A等位基因(P校正 = 0.027)、AA和AC基因型(OR分别为10.9和9.0)以及TAA单倍型(分别为rs2205849、rs5361和rs1805193;P = 0.03)与RAS存在显著关联。其他SNP均未显示出显著关联。

结论

这是首次报道E-选择素rs5361多态性的A等位基因、AA和AC基因型的遗传与RAS风险增加有关。需要在不同患者队列中进行进一步研究以证实这种关联,功能分析可能会阐明这种关联的生物学意义。

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