Polymorphisms and phenotypic analysis of cytochrome P450 3A4 in the Uygur population in northwest China.

PURPOSE: Genetic polymorphisms in CYP3A4 can change its activity to a certain degree, thus leading to differences among different populations in drug efficacy or adverse drug reactions. METHODS: The study was intended to validate the genetic polymorphisms in CYP3A4 in Uygur Chinese population, we sequenced and screened for genetic variants including 5'UTR, promoters, exons, introns, and 3'UTR region of the whole CYP3A4 gene in 100 unrelated, healthy. RESULTS: Twenty-one genetic polymorphisms in CYP3A4, and nine of them were novel. We detected CYP3A4*8, a putative poor-metabolizer allele, with the frequency of 0.5% in Uygur population. Tfsitescan revealed that the density of transcription factor varied in the different promoter regions, among which some were key regions for transcription factor binding. CONCLUSION: our results provide basic information about CPY3A4 alleles in Uygur and suggest that the enzymatic activities of CPY3A4 may differ among the diverse ethnic populations of China.

Delftia deserti sp. nov., isolated from a desert soil sample.

A Gram-staining negative, short rod, motile, light brownish-pigmented bacterial strain, designated YIM Y792(T), was isolated from a soil sample taken from Turpan desert in Xinjiang Uyghur Autonomous Region, north-western China. Phylogenetic analysis indicated that strain YIM Y792(T) belongs to the genus Delftia. Strain YIM Y792(T) shared highest 16S rRNA gene sequence similarities with Delftia lacustris DSM 21246(T) (93.96 %), Delftia tsuruhatensis NBRC 16741(T) (93.74 %), and Delftia acidovorans NBRC 14950(T) (93.62 %). Growth of the strain YIM Y792(T) was found to occur at 20-45 °C (optimum at 30 °C), pH 6.0-9.0 (optimum at pH 7.0), and salinities of 0-3.0 % NaCl (optimum at 1.0 %). The new bacterium exhibits typical chemotaxonomic features of the genus Delftia with ubiqinone-8 (Q-8) as the predominant quinone and C16:0, Summed feature 3, Summed Feature 8 as major fatty acids (>10 %). The polar lipids were found to consist of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, glycolipid, two unidentified phospholipids and one unidentified lipid. The G+C content of the genomic DNA of strain YIM Y792(T) was found to be 70.3 mol%. The DNA-DNA relatedness values between strain YIM Y792(T) and D. lacustris DSM 21246(T), D. tsuruhatensis NBRC16741(T), D. acidovorans NBRC14950(T) were 35.5 ± 2.0, 17.1 ± 1.8, 26.2 ± 2.0 %. Based on the phylogenetic, chemotaxonomic and phenotypic data presented here, we propose a novel species with the name Delftia desertisoli sp. nov. The type strain is YIM Y792(T) (=KCTC 42377(T) = JCM 30639(T)).

Genetic polymorphisms of VIP variants in the Tajik ethnic group of northwest China.

BACKGROUND: Individual response to medications varies significantly among different populations, and great progress in understanding the molecular basis of drug action has been made in the past 50 years. The field of pharmacogenomics seeks to elucidate inherited differences in drug disposition and effects. While we know that different populations and ethnic groups are genetically heterogeneous, we have not found any pharmacogenomics information regarding minority groups, such as the Tajik ethnic group in northwest China. RESULTS: We genotyped 85 Very Important Pharmacogene (VIP) variants selected from PharmGKB in 100 unrelated, healthy Tajiks from the Xinjiang Uygur Autonomous Region and compared our data with HapMap data from four major populations around the world: Han Chinese (CHB), Japanese in Tokyo (JPT), Utah Residents with Northern and Western European Ancestry (CEU), and Yorubia in Ibadan, Nigeria (YRI). We found that Tajiks differed from CHB, JPT and YRI in 30, 32, and 32 of the selected VIP genotypes respectively (p < 0.005), while differences between Tajiks and CEU were found in only 6 of the genotypes (p < 0.005). Haplotype analysis also demonstrated differences between the Tajiks and the other four populations. CONCLUSION: Our results contribute to the pharmacogenomics database of the Tajik ethnic group and provide a theoretical basis for safer drug administration that may be useful for diagnosing and treating disease in this population.

Genetic polymorphisms of pharmacogenomic VIP variants in the Kyrgyz population from northwest China.

Pharmacogenomic variant information is well known for major human populations; however, this information is less commonly studied in minorities. In the present study, we genotyped 85 very important pharmacogenetic (VIP) variants (selected from the PharmGKB database) in the Kyrgyz population and compared our data with other four major human populations including Han Chinese in Beijing, China (CHB), the Japanese in Tokyo, Japan (JPT), a northern and western Europe population (CEU), and the Yoruba in Ibadan, Nigeria (YRI). There were 13, 12 and 16 of the selected VIP variant genotype frequencies in the Kyrgyz which differed from those of the CHB, JPT and CEU, respectively (p<0.005). In the YRI, there were 32 different variants, compared to the Kyrgyz (p<0.005). Genotype frequencies of ADH1B, AHR, CYP3A5, PTGS2, VDR, and VKORC1 in the Kyrgyz differed widely from those in the four populations. Haplotype analyses also showed differences among the Kyrgyz and the other four populations. Our results complement the information provided by the database of pharmacogenomics on Kyrgyz. We provide a theoretical basis for safer drug administration and individualized treatment plans for the Kyrgyz. We also provide a template for the study of pharmacogenomics in various ethnic minority groups in China.