title: Differences in 5-hydroxytryptamine-3B haplotype frequencies between Asians and Caucasians.
abstract: BACKGROUND
  The 5-hydroxytryptamine (5-HT3) receptor is a ligand-operated ion channel with five different receptor subunits (5-HT3A, B, C, D, and E) found in humans. Activation of 5-HT3 receptors influences various effects such as drug-induced emesis and causes behavioral problems such as anxiety, depression and cognitive disorders. To explore interethnic differences in the response to 5-HT3 antagonists, we studied haplotype frequencies in the gene encoding the 5-HT3B receptor in Asians and Caucasians.
  
  
  METHODS
  Three single nucleotide polymorphisms (SNPs) of the 5-HT3B receptor gene, i.e., deletion AAG at the 5'-UTR position, 18792A>G at the intron position, and 46698G>A at the 3' near gene position, were selected and genotyped in 165 Indonesian cancer patients and 188 Caucasian healthy volunteers. Haplotypes were set with gPlink, whereas the differences in haplotype frequencies between Indonesians and Caucasians were compared using multivariate analysis.
  
  
  RESULTS
  The haplotype profiles based on the deletion AAG, 18792A>G and 46698G>A were AAGAA, AAGAG, AAGGG, and deletion AG in both Indonesians and Caucasians. The frequency of the AAGAG haplotype was 54.8% in Indonesians and 39.9% in Caucasians (p<0.05). The frequency of the AAGGG haplotype was 14.3% in Indonesians and 29.3% in Caucasians. Moreover, there were significant differences in the frequencies of haplotype pairs between Indonesians and Caucasians (p<0.001).
  
  
  CONCLUSIONS
  Indonesian cancer patients had significantly different AAGAG and AAGGG haplotype frequencies of the gene encoding the 5-HT3B receptor compared to healthy Caucasians. This finding could be useful for understanding interethnic differences in the response to drugs targeting the 5-HT3B receptor in cancer-treatment-related emesis.
authors.affiliation: Department of Pharmacy, Ahmad Dahlan University, Yogyakarta - Indonesia.
authors.forename: Dyah A
authors.initials: DA
authors.lastname: Perwitasari
authors.forename: Robert J H M
authors.initials: RJ
authors.lastname: van der Straaten
authors.forename: Mustofa
authors.initials: M
authors.lastname: Mustofa
authors.forename: Judith A M
authors.initials: JA
authors.lastname: Wessels
authors.forename: Hans
authors.initials: H
authors.lastname: Gelderblom
authors.forename: Henk-Jan
authors.initials: HJ
authors.lastname: Guchelaar
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011985:Receptors, Serotonin / Q000235:genetics*; D017384:Sequence Deletion; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000009:adverse effects / Q000494:pharmacology; D014839:Vomiting / Q000139:chemically induced; D044465:White People / Q000235:genetics*; D055815:Young Adult
chemical_list: D011985:Receptors, Serotonin; D058831:Serotonin 5-HT3 Receptor Antagonists