Association Analysis of NAT2 590 G/A Gene Polymorphism in Smokers with Periodontitis: A Case–Control Study

Abstract Aim: Periodontitis is a chronic inflammatory disease modulated by genetic and environmental factors. Arylamine N-acetyltransferase2 (NAT2) plays a key role in detoxifying harmful compounds from cigarette smoke. NAT2 polymorphisms, particularly at 590 G/A, may alter acetylation capacity, potentially affecting disease susceptibility. This study was aimed to investigate the association between NAT2 590 G/A gene polymorphism and periodontitis among smokers and non-smokers in an ethnic Tamil population from South India. Materials and Methods: The case–control study was conducted with 180 male participants divided into three groups ( n = 60 each): smokers with healthy periodontium (controls), smokers with periodontitis (test group 1), and non-smokers with periodontitis (test group 2). Periodontal parameters (probing pocket depth, clinical attachment loss, PlI, and mSBI) were recorded. NAT2 genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism. Genotype and allele frequencies were analyzed using the chi-square tests. Odds ratios (ORs) were calculated to assess the strength of associations. Results: Heterozygous GA genotype was more prevalent in both periodontitis groups (55% and 60%) than in controls (38%). The GA genotype was significantly associated with periodontitis in smokers (OR = 2.34; P = 0.03) and non-smokers (OR = 2.85; P = 0.009). Allele A was more frequent in test groups (40–41%) than in controls (29%) and showed a modest association (OR = 1.67–1.73; P ≤ 0.05). No additive effect of smoking was observed. Conclusion: The NAT2 590 G/A polymorphism is significantly associated with periodontitis in the studied population. Smoking did not amplify the genetic risk, suggesting a primarily genetic influence in this ethnic cohort. Further studies are warranted to validate gene–environment interactions in larger and more diverse populations.