Fogorvosi szemle, 2007 (100. évfolyam, 1-6. szám)

2007-10-01 / 5. szám

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FOGORVOSI SZEMLE ■ 100. évf. 5. sz. 2007.

tigated, we observed only wild type monozygotes and heterozygotes. Because of the appearance of the rare alleles in each gene polymorphism investigated, it is really reasonable to do further studies comparing control and patient groups.

In Figure 3 inserts I and J show two polymorphisms (-1031 G/A, -912 C/T) of the PAX9 transcription factor gene that can be potentially associated to the development of hypodontia. The PAX9 gene product size is 202 bp. This PCR product can be digested by Hael- II restriction endonuclease treatment yielding 26 and 176 bp secondary products in the case of G allele, while it is not digested when the A allele is present (I). The treatment of the same PCR product by the Msei restriction endonuclease gives information about the allele at the -912 position. If the C allele is present at this position 45 and 157 bp fragments can be seen, while T allele results in 45 and 144 bp fragments in the electrophoretic picture (J). The smaller, 45 bp fragments cannot be seen on the photo because of technical reasons. These data clearly suggest that the two investigated positions of the PAX9 gene exhibits variabilities in the Hungarian population as well.

Discussion

The purpose of our study is to map single nucleotide polymorphisms as genetic-genomic risk factors in periodontitis and hypodontia, a congenital dental disorder, in the Hungarian population.

The number of genes that might play a role as risk factor in the development of periodontitis can be estimated at the level of several dozens, or even one hundred or more. It is important to note, however, that the number and the types of risk factors are not necessarily the same in different ethnic groups. In addition, their appearance in phenotype also depends on environmental factors affecting the population (geneenvironment interaction) [4]. Several studies aimed to establish a relationship between the severity of periodontitis and the polymorphisms of inflammatory mediators, cytokines and their receptors [16] [17] [18]. Up till now most studies investigated the interleukin-1 (IL-1) genes and the tumor necrosis factor-a (TNF-a) gene as genetic risk factors in periodontitis [19] [20]. According to the first transversal study, the polymorphisms of IL-1 genes (IL-1 a -889, IL-1 ß +3953) in Caucasian, non-smoking population show strong correlation with the severity of the disease. Such concomitant appearance is called IL-1 composite polymorphism in accordance with the definition of Kornman [19], Further investigations, however, provided evidence that these polymorphisms are significant only when other damaging factors, such as smoking, are present. These results suggest that the individual risk factors are not only additive, but the genetic and environmental factors may interact and strongly potentiate the actual biological

response. The presently available data support the assumption that the IL-1 gene polymorphisms in certain ethnic groups are much weaker risk factors than in others [17],

Figure 2

Degraded and intact DNA after gel electrophoresis. Samples 1,2 and 3 show the electrophoretic picture of degraded DNA. DNA samples 4, 5 and 6 can be regarded as intact.

Results regarding the periodontal role of TNF-a gene polymorphisms are even more controversial. One study, in which four polymorphisms of TNF-a gene were investigated, shows that TNF-a is not a risk factor in the development of periodontitis [20], On the other hand, several studies suggest that the IL-1 and TNF-a gene alleles together in certain combination are potential risk factors on complex inflammatory diseases. In addition, the role of other cytokines (e.g. IL-6, IL-10) and non-cytokines (e.g. TLR-4) should also be considered. The detailed review of these is over the scope of the present paper. But we have to note that the key issue is probably not the single polymorphism of the individual genes but rather the coincidence and the complexity of multiple SNPs.

In the present study among the investigated eight polymorphisms of six genes, IL-1 a, IL-1 ß, IL-6, IL-10, TLR-4, and TNF-a, we found homozygotes even for the rare alleles in six cases, while in two others the rare allele appeared only in heterozygous form. All of these polymorphisms are potential risk factors in the development of the different forms of periodontitis [14, 20, 21], Further population level studies are necessary to get information about the significance of these factors in the Hungarian population to understand genetic/genomic background of the disease.

According to the available published data, most probably several mutations of transcription factors Msx1 and Pax9 may lead to hypodontia. Msx1 is normally expressed in dental mesenchyme, but it is not present in the dental epithelium during the development of bud cap and bell stages of tooth development [22], Most probably, the mutations of the coding region of Msx1