A genetic association study of single nucleotide polymorphisms in FGFR1OP2/wit3.0 and long-term atrophy of edentulous mandible.
A genetic association study of single nucleotide polymorphisms in FGFR1OP2/wit3.0 and long-term atrophy of edentulous mandible.
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DOI：
10.1371/journal.pone.0016204
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发表时间：
2011-01-19
期刊：
影响因子：
3.7
通讯作者：
Nishimura I
中科院分区：
文献类型：
--
作者：
Suwanwela J;Lee J;Lin A;Ucer TC;Devlin H;Sinsheimer J;Garrett NR;Nishimura I
拔牙后，牙槽骨外表面发生不同速率的吸收，部分患者出现颌骨过度萎缩。覆盖在萎缩颌骨上的口腔黏膜异常薄；因此，我们假设颌骨过度萎缩可能与口腔黏膜异常收缩有关。FGFR1OP2/wit3.0是一种最初在口腔伤口成纤维细胞中发现的细胞骨架分子，已被证明可诱导拔牙后口腔黏膜收缩。本研究探讨了FGFR1OP2/wit3.0的单核苷酸多态性（snp）与无牙下颌骨过度萎缩之间的遗传关系。首先，检测8例受试者拔牙前后牙龈组织中FGFR1OP2/wit3.0的表达情况。原位杂交显示，所有受试者术后口腔黏膜组织中FGFR1OP2/wit3.0表达均升高；然而，在8名受试者中，有3名受试者观察到显著高水平的FGFR1OP2/wit3.0。在另一项研究中，招募了20名长期无牙受试者（66.4±9.4岁）。FGFR1OP2/ with3.0等位基因的标签snp通过Taqman-based聚合酶链反应测定。下颌骨高度根据美国修复医师学会（American College of Prosthodontists， ACP）方案确定。ACP分类发现高度萎缩组存在rs840869或rs859024小等位基因（卡方检验，p = 0.0384和p = 0.0565; Fisher’s Exact, p = 0.0515和p = 0.2604）。线性回归分析显示，rs859024与骨高降低存在相关性（Mann-Whitney, p = 0.06）。rs840869和rs859024小等位基因的平均骨高（分别为10.6±3.2 mm和9.6±3.2 mm）显著小于大等位基因的平均骨高（14.2±4.5 mm, p<0.05）。携带rs840869或rs859024等位基因的患者与无牙下颌骨过度萎缩相关。本研究可为建立牙拔术后颌骨萎缩易感个体的遗传标记提供依据。
After dental extraction, the external surface of alveolar bone undergoes resorption at various rates, and a group of patients develop excessive jawbone atrophy. Oral mucosa overlying the atrophied jawbone is unusually thin; therefore, we have hypothesized that excessive jawbone atrophy may be associated with abnormal oral mucosa contraction. FGFR1OP2/wit3.0, a cytoskeleton molecule initially identified in oral wound fibroblasts, has been shown to induce oral mucosa contraction after dental extraction. This study examined the genetic association between single nucleotide polymorphisms (SNPs) of FGFR1OP2/wit3.0 and excessive atrophy of edentulous mandible. First, the expression of FGFR1OP2/wit3.0 was determined in gingival tissues of 8 subjects before and after dental extraction. In situ hybridization revealed that all subject increased FGFR1OP2/wit3.0 expression in the post-operative oral mucosa tissues; however, significantly high levels of FGFR1OP2/wit3.0 were observed in 3 out of 8 subjects. In a separate study, 20 long-term edentulous subjects (66.4±9.4 years) were recruited. Tag-SNPs in the FGFR1OP2/wit3.0 allele were determined by Taqman-based polymerase chain reaction. The mandibular bone height was determined following the American College of Prosthodontists (ACP) protocol. Subjects with minor allele of rs840869 or rs859024 were found in the highly atrophied group by the ACP classification (Chi square test, p = 0.0384 and p = 0.0565, respectively; Fisher's Exact, p = 0.0515 and p = 0.2604, respectively). The linear regression analysis indicated a suggestive association between rs859024 and the decreased bone heights (Mann-Whitney, p = 0.06). The average bone height of the subjects with rs840869 or rs859024 minor alleles (10.6±3.2 mm and 9.6±3.2 mm, respectively) was significantly smaller than that of those subjects with the major alleles (14.2±4.5 mm, p<0.05). The patients with the minor allele of rs840869 or rs859024 were associated with excessive atrophy of edentulous mandible. This study may provide the basis for a genetic marker identifying susceptible individuals to develop jawbone atrophy after dental extraction.