Association Of The Metabolizing Enzymes Genetic Polymorphisms With The Susceptibility To Severe Chronic Periodontitis

Periodontitis is a chronic, bacterially infected inflammation of the periodontium. Periodontal diseases are viewed today as multifactorial problems initiated by the bacteria but significantly modified by the host's response to bacterial plaque. Many studies have shown that genetic factors play an important role in the onset of periodontitis. The individual susceptibility to periodontal diseases is the result of interactions of multiple genetic and environmental risk factors.Epidemiological studies in different populations have shown that smoking is a risk factor for periodontal disease, especially for severe periodontitis. The noxious substances derived from tobacco may have direct or indirect effects on periodontitis. Besides the xenobiotic substances in tobacco, others ectogenetic or endogenous compounds such as toxic metabolites from periodontal microorganisms (indole, amines, etc.), hormone, prostaglandin, contribute to the periodontal inflammatory process. All these substances are transformed in vivo by metabolizing enzymes, both in bioactivation and detoxification. Metabolizing enzymes contain two main types of enzymes: the phase-I oxidative enzymes, which are mainly cytochromes P-450 (CYP), andphase-II conjugating enzymes such as glutathione S-transferases (GSTs), N-acetyltransferase (NATs). Metabolic activity to foreign substances by metabolizing enzymes determines the individual susceptibility to toxicity of these compounds. Evidences support that there is a high concordance between genetic polymorphisms and metabolic capacities of metabolizing enzymes. We hypothesize that the genetic polymorphisms of metabolizing enzymes may contribute to an increased risk for periodontitis, especially in subjects exposed to cigarette smoke or other xenobiotics.The purpose of this study is to assess the relationship between the genetic polymorphisms of CYP1A1, GSTM1, GSTT1, NAT2 enzymes and severe chronic periodontitis in Chinese Han nationality. DNA samples were collected with buccal swabs from 112 subjects with severe chronic periodontitis and 78 periodontal healthy controls. The genetic polymorphisms of CYP1A1, GSTM1, GSTT1 and NAT2 were determined using allele-specific polymerase chain reaction (AS-PCR), multiplex differential PCR (MD-PCR) and polymerase chain reaction/restriction fragment length polymorphisms (PCP-RFLP). The frequencies of alleles and genotypes were compared between the patients and the controls.The results showed that:1, Alelle frequencies of the CYP1A1 Mspl, Ile/Val in healthy controls of Han nationality in Sichuan were 0.43 and 0.30, respectively. The Mspl mutation allele and genotype frequencies were significantly decreased in patients with severe chronic periodontitis compared with the reference population (p<0.05, OR<1). The result indicated that Mspl wild genotype was relative to an increased risk for periodontitis. Similar results in statistically analysis with Ile/Val allele and genotype frequencies were reached.Furthermore, stratified analysis suggested an interaction between cigarette smoking and CYP1A1 Mspl or Ile/Val wild genotype. Smoking and CYP1A1 wild genotype together possibly increased the risk further.2, In healthy controls, the frequencies of GSTMlnuU genotype and GSTTlnulI genotype were 41.03% and 47.44%, respectively. No significant association between GSTMlnuU genotype or GSTTlnulI genotype and severe chronic periodontitis was found. But combined genotype GSTMlnuU and GSTTlnulI was associated significantly with severe CP (OR=2.49, PO.05). Furthermore, stratified analysis suggested that in smokers, GSTMlnuU genotype or GSTTlnulI genotype alone was also associated significantly with severe CP (PO.05).3, The frequencies of alleles ml, m2 and m3 of NAT2 in severe CP patients were 10.71%, 40.63% and 14.73%, respectively, while 8.34%, 30.12% and 14.10% in controls. The difference in frequency of allele m2 between the two groups was statistically significant (P=0.040<0.05)o The frequency of slow acetylator genotypes in patients was 45.54%, while 26.92% in controls. The difference was statistically significant (P=0.009<0.05), the odds ratio being 2.269 (95%CI=1.217-4.233). Stratified analysis suggested an interaction between cigarette smoking and slow acetylator genotype. Smoking and slow acetylator genotype together possibly increased the risk further.The results indicate that certain genetic polymorphisms of metabolizing enzymes were associated with the susceptibility to severe chronic periodontitis in Chinese Han nationality.