Single Nucleotide Polymorphisms in HIF-1α Gene and Residual Ridge Resorption (RRR) of Mandible in Korean Population

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-1 alpha 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-1 alpha 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-1 alpha 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.