AIMS: To investigate the frequency of the single nucleotide polymorphism @entity7658 in exon 26 of the @entity1262 gene in Asians and to determine the functional significance of this SNP with the clinical pharmacokinetics of oral @entity205 (Neoral) in 10 stable heart transplant @entity1 . METHODS: The @entity1262 @entity7658 polymorphism was investigated in 290 healthy Asian subjects (98 Chinese, 99 Malays and 93 Indians). We also compared the @entity1262 polymorphism between the Asian population studied here and the published data on Africans and Caucasians. The clinical relevance of this SNP on oral bioavailability of a known @entity7895 substrate, @entity205 , was assessed in 10 stable Chinese heart transplant @entity1 . RESULTS: The homozygous TT genotype was observed in 32%, 28% and 43% of Chinese, Malays and Indians. The homozygous CC genotype was found in 25% of Chinese and Malays compared with 18% of Indians. The Indians had a lower frequency of the C allele [0.38 (0.31-0.45)] compared with the Chinese [0.46 (0.39-0.53)] and Malays [0.48 (0.42-0.55)]. Chi-squared test showed that the distribution of allele frequencies between the Malays and Indians differed significantly (P = 0.04). In this Asian population, the overall distribution of genotypes (CC, CT and TT) and allele frequencies were significantly different from those in Africans (P < 0.001). The results were also significant when the Chinese, Malays and Indians were compared separately with the African group (P < 0.001). Compared with the Caucasian data, the overall distribution of genotype and allele frequencies in the Asian population were also significantly different (P < or = 0.05). However, when each Asian ethnic group was compared separately with the Caucasians, only the Indians were found to be significantly different (P < or = 0.004). Genotypic-phenotypic correlations of this SNP were assessed in 10 stable Chinese heart transplant @entity1 . The median AUC(0,4 h) was 11% lower in @entity1 with CC genotype compared with subjects with TT genotype. However, the interpatient variability in AUC(0,4 h) was high in @entity1 , especially in those with CC genotype. CONCLUSIONS: The distribution of the SNP @entity7658 in exon 26 in the Chinese and Malay population was found to be similar to the Caucasians whereas the Indians were different. The Asian population also differed significantly from the African and Caucasian population in the distribution of the @entity7658 SNP. The low frequency of the T allele in the Indian population implies lower expression of @entity7895 and may have important therapeutic and prognostic implications for use of @entity7895 dependent drugs in individuals of Indian origin.

Frequency of XXXX single nucleotide @entity1262 genetic polymorphism in an Asian population: phenotypic-genotypic correlates.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity1262 :: ('5243', 'Gene') :: ['MDR1'] @entity205 :: ('MESH:D016572', 'Chemical') :: ['cyclosporin'] @entity7895 :: ('283871', 'Gene') :: ['P-gp'] @entity7658 :: ('c|SUB|C|3435|T', 'DNAMutation') :: ['C3435T']
@entity7658 :: (c|SUB|C|3435|T,DNAMutation) :: ['C3435T']
