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Tryptophan hydroxylase (TPH) gene which encodes the first rate-limiting enzyme in the serotonin biosynthesis pathway is one of the leading candidate genes in the etiology of the most common gastrointestinal (GI) disease, the irritable bowel syndrome (IBS). SNPs in the gene would distract the serotonergic function which led to the susceptibility to the syndrome. This study is aimed to determine the genotype distributions and allele frequencies of the three SNPs from two TPH genes, TPH1 and TPH2 genes among healthy, unrelated Malays in Malaysia. Nested-multiplex-allele specific PCR (NMAS-PCR) was subjected to 404 archived Malays' DNA to genotype rs211105, rs4537731 and rs4570625 variants following the validation of the obtained genotyping results through the direct Sanger sequencing. Results showed that the genotype frequencies of AA in rs211105 and rs4537731 among Malays were 59.2 and 51.5%. The heterozygous of GT was found to be slightly higher than GG with 47.5 to 43.3% in rs4570625. Meanwhile, the mutant allele frequencies of rs211105, G and rs4537731, T were relatively comparable with 30.3 to 33.0% accordingly. Concurrently, no departure of HWE was detected except in rs4537731. This study described low frequencies of TPH1 and TPH2 SNPs mutant variants associated with the IBS among unrelated, healthy Malays. Data generated from this study is important to enhance our knowledge of the association between IBS pharmacogenetic profiles and ethnic differences. Future studies on Malaysian IBS patients are recommended to determine the influence of rs211105, rs4537731 and rs4570625 on the syndrome locally. [ABSTRACT FROM AUTHOR]