Analysis of single nucleotide polymorphisms in the 5'-flanking region of tumor necrosis factor-alpha gene in Japanese patients with early-onset periodontitis

Background: Early-onset periodontitis (EOP) is considered to have a genetic basis, which has not been clearly defined. The tumor necrosis factor-alpha (TNF-alpha) gene polymorphism as one of the genetic factors may influence the expression of several chronic inflammatory diseases. The aim of the pre sent study was to evaluate whether the polymorphisms in the 5'-flanking reg ion of the TNF-alpha gene are associated with Japanese EOP patients. Methods: Forty-six Japanese, generalized EOP (G-EOP) patients and 104 Japan ese healthy subjects were identified according to established clinical crit eria. Twenty healthy subjects were analyzed by nucleotide sequence to scree n polymorphisms of the 5'-flanking region of the TNF-alpha gene. Then, all subjects were analyzed by polymerase chain reaction and sequencespecific ol igonucleotide probe (SSOP) methods. Results: We determined 5 single nucleotide polymorphisms at positions - 103 1 (T/C), -863 (C/A), -857 (C/T), -308 (G/A), and -238 (G/A) in the 5'-flank ing region of the TNF-alpha gene. There were no significant differences in the genotype and allele frequency when we compared G-EOP patients to health y subjects. Because the frequency of polymorphic alleles at positions -308 and -238 was very low in this study population, we demonstrated the existen ce of 4 detected haplotypes and 6 detected genotypes concerning 3 single nu cleotide polymorphisms (-1031, -863, and -857). The frequency of the H1/H3 (TCC/TCT)-detected genotype tended to decrease in G-EOP patients compared t o healthy subjects, but was not statistically significant. Conclusion: These findings suggest there is no significant association betw een polymorphisms in the 5'-flanking region of the TNF-alpha gene and susce ptibility to G-EOP in Japanese patients.