Rasmaizatul Akma ROSDİ, Nurfadhlina MUSA, Zalına ZAHARI, Mohd Khairi ZAHRİ @ JOHARİ, Mulham ALFATAMA, Boon Yin KHOO

The prevalence of TPH1 and TPH2 genetic polymorphisms susceptible to irritable bowel syndrome (IBS) among unrelated, healthy Malays in Malaysia

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). The 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 genotyping results obtained through the direct Sanger sequencing. Results showed the genotype frequencies of AA in rs211105 and rs4537731 among Malays was 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 considerably 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 on the association of IBS pharmacogenetic profiles and the ethnic differences. Future studies on Malaysian IBS patients are recommended to determine the influence of rs211105, rs4537731 and rs4570625 to the syndrome locally.

Keywords:

Irritable bowel syndrome IBS, rs211105, rs4537731, rs4570625, Malay, Malaysia,

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