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Single nucleotide polymorphisms in HIF-1α gene and residual ridge resorption (RRR) of mandible in Korean population.

ABSTRACT: Tooth extraction is a routine surgical procedure in dental treatment. As a wound healing process after tooth extraction, a saddle-shaped residual ridge forms due to bone formation in the extraction socket and localized bone resorption on the external surface of the jawbone. The residual ridge is subjected to continuous bone resorption with substantial differences among individuals. In some cases, it results in excessive bone atrophy, which complicates dental restorative treatment. This unique oral wound healing process may be influenced by factors that are specific to oral tissue. HIF expression is different in oral wound healing compared to that of skin wounds. The objective of this study was to examine a genetic association between SNP of the HIF-1α gene, which is known to have high genetic diversity, and the residual ridge resorption (RRR). Two hundred and two Korean subjects (70.80 ± 9.40 years) with partially or completely edentulous mandible were recruited, and edentulous mandibular bone height was measured following the protocol of the American College of Prosthodontists. The HIF-1α allele was directly sequenced in 24 subjects resulting in the variants over 5% frequency in 95% likelihood, whereas tag-SNPs were selected to perform analysis for the remaining population. Student's t-test and ANOVA were used for statistical analysis to examine the association between the SNPs and the RRR. Four novel variants were discovered, and a minor allele of rs11549467 was associated with the RRR of the subjects (p = 0.028). rs11549467 increases HIF-1α transactivity, enhancing angiogenesis and increasing new vessel formation. Thus, rs11549467 may play an important role in the disturbed bone remodeling balance resulting in RRR. Results of this study may be useful in developing novel genetic diagnostic tests and identifying Koreans susceptible to developing excessive jawbone atrophy after dental extraction. Most importantly, early screening using genetic information will rescue susceptible patients from the vulnerable situation of excessive jawbone atrophy where no effective prosthetic treatment is available.

SUBMITTER: Paek J

PROVIDER: S-EPMC8750342 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description: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.

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Single nucleotide polymorphisms in HIF-1α gene and residual ridge resorption (RRR) of mandible in Korean population.

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