Introduction:PTGS2 and DEFB1 single nucleotide polymorphisms (SNP) have been validated to be associated with chronic periodontitis (CP) in European, Japanese and Chinese populations. Polymorphisms of these genes play a role in the pathogenesis of CP. Thus far, no study has been done on the Malay ethnic group. Hence, this study assessed the allele and genotype frequencies of PTGS2 and DEFB1 variants in subjects with chronic periodontitis and healthy individuals in Malaysian Malays. Methods: Malay CP subjects and periodontally-healthy controls were obtained from Malaysian Periodontal Database and Biobanking system (MPDBS) for this case-control study. Diagnosis for cas-es was based on case definition by Eke et al (2012). DNA samples were genotyped for 4 candidate SNPs, rs689466, rs5275, rs20417 (PTGS2) and rs1047031 (DEFB1). Genotyping was carried out using Taqman genotyping method. The association between SNPs and study groups were assessed using logistic regression analysis. Results: DNA sam-ples from 140 individuals, 76 CP cases and 64 healthy controls were genotyped. Logistic regression results demon-strated that rs689466 for PTGS2 gene was associated with CP susceptibility in the Malay study group (p=0.03; OR: 1.80; 95% CI=1.05-3.07). The dominant and additive model test showed significant association with rs689466 (C/T) (pdominant-adjusted=0.02; OR: 2.22; 95% CI=1.11-4.43;padditive-adjusted=0.03; OR:1.85; 95% CI=1.07-3.19) after controlling for age and smoking. However, no significant association with CP was observed with other SNPs. Conclusion: The results suggest that rs689466 of PTGS2 gene may contribute to CP susceptibility in Malaysian Malay population in our preliminary study.