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Huai-Rong Luo

Publications and source records attributed to Huai-Rong Luo.

11 recordsLinked to original sources
PubMed2006

Genetic polymorphism of cytochrome P450 2C19 in Mexican Americans: a cross-ethnic comparative study.

OBJECTIVES: Our objectives were to investigate cytochrome P450 (CYP) 2C19 polymorphism in Mexican Americans and compare the findings with those in 4 other ethnic groups. METHODS: The CYP2C19 genotype (n = 346) and S-mephenytoin hydroxylation phenotype (n = 220) were studied in a Mexican American population from Los Angeles County. Another 4 ethnic groups, African Americans (n = 236), whites (n = 273), East Asians (n = 161), and Southeast Asians (n = 80), were also recruited from Los Angeles County and genotyped and phenotyped for CYP2C19. RESULTS: The frequencies of CYP2C19*2 and *3 were 9.7% and 0.1%, respectively, in Mexican Americans, which were lower than those of the other 4 ethnic groups, ranging from 12.7% to 31.2% and 0.8% to 9.6%, respectively (P <or= .035). Seven Mexican American subjects were phenotyped as poor metabolizers. Thus the frequency of poor metabolizers in the Mexican American subjects was 3.2% (95% confidence interval, 0%-11.9%), which is similar to that of African Americans (5.4%) and whites (5.0%) and lower than that of East Asians (16.7%; P < .001) and Southeast Asians (23.9%; P < .001). Of the 7 poor metabolizers who were also genotyped, 2 were homozygous for the CYP2C19*2 alleles. CYP2C19*4, *5, *6, *7, and *8 were studied and did not account for the unexplained finding. The number of functional alleles among the extensive metabolizers correlated with the phenotype, suggesting a gene-dosage effect in Mexican Americans. CONCLUSIONS: This is the first study to investigate CYP2C19 polymorphism in Mexican Americans. The frequencies of the CYP2C19*2 and *3 alleles in Mexican Americans were found to be significantly lower than in other ethnic groups. This genotypic pattern might be responsible for the lower rate of poor metabolizers in Mexican Americans compared with other ethnic groups.

Adult↗
PubMed2006

Retinoids activate the RXR/SXR-mediated pathway and induce the endogenous CYP3A4 activity in Huh7 human hepatoma cells.

Steroid and xenobiotic receptor (SXR) or human pregnane X receptor (hPXR) dimerizes with retinoid X receptor (RXR) and regulates the transcription of genes encoding xenobiotic-metabolizing enzymes such as CYP3A4. Rifampin, the classical activator of CYP3A4, binds to SXR directly. It is unclear whether various natural and synthetic retinoids can regulate the expression of CYP3A4. To evaluate the effects of retinoids on the RXR/SXR-mediated pathway, transient transfection assays were performed on both CV-1 and human hepatoma Huh7 cells using a reporter construct containing multiple RXR/SXR consensus binding elements (an everted repeat with a 6-nucleotide spacer, ER-6). The results revealed that eight out of 13 retinoids screened significantly induced the RXR/SXR-mediated pathway in Huh7 cells. At an equal molar concentration, the acid forms (9-cis-RA, 13-cis-RA, and all-trans-RA) or aldehyde, the direct precursor of acid (9-cis-retinal and 13-cis-retinal), exhibited a greater or similar potency than rifampin. Depending on the ligands, RXR may serve as a silent or an active partner of SXR. Additionally, retinoids can increase CYP3A4 enzyme activity in Huh7 cells. To further evaluate the potential drug-drug interactions, which may be caused by retinoids, Huh7 cells were pretreated with 9-cis-RA and followed by acetaminophen. We showed that 9-cis-RA enhanced the covalent binding of N-acetyl-p-quinoneimine, a toxic intermediate of acetaminophen produced by phase I enzymes oxidation. This result suggested that drug-drug interaction might occur between 9-cis-RA and acetaminophen in human liver cells. Taken together, retinoids activate the RXR/SXR-mediated pathway and regulate the expression of CYP3A4. Thus, retinoids potentially can cause drug-drug interactions when they are administered with other CYP3A4 substrates.

Blotting, Northern↗
PubMed2005

Identification of CYP2D6 impaired functional alleles in Mexican Americans.

OBJECTIVES: To extend the genotyping analysis of the CYP2D6 gene and further explain variability of CYP2D6 activity in Mexican Americans by genetic factors. METHODS: CYP2D6 gene sequence variations associated with *6, *7, *8, *9, *11, *14, *29, *41, *45, and *46 alleles as well as the 2988G>A SNP were examined in 264 Mexican Americans; 236 had previously been phenotyped with dextromethorphan. All subjects were previously genotyped for CYP2D6*2, *3, *4, *5, *10, *17, and the presence of a gene duplication. Associations between genotype and CYP2D6 activity were determined. RESULTS: Mexican Americans revealed a high frequency of functional alleles (CYP2D6*1 and *2; 73.1%), followed by CYP2D6*4 (non-functional, 10.0%) and the reduced-function allele *41 (9.5%). The frequencies of CYP2D6*5, *6, *9, *10, duplication, and 2988A were 1.7%, 0.4%, 1.1%, 2.8%, 0.8%, and 5.7%, respectively. CYP2D6*3, *17, and *29 were found only in one individual (CYP2D6*2/*3, *1/*17, and *4/*29), while CYP2D6*7, *8, *11, *14, *45, and *46 were absent in this study population. Decreased CYP2D6 activity was more accurately predicted by the presence *41[-1584C] compared to *41[2988A]. One genotype/phenotype discordant subject was resolved by the presence of a CYP2D6*6 allele (*4/*6), while two other cases remained discordant (*41/*41 and *1/*1). CONCLUSIONS: The CYP2D6*4, *5, and *6 null alleles along the reduced function alleles *9, *10, and *41 are the major cause for diminished dextromethorphan oxidative capacity in Mexican Americans. These findings may have implications for the safety and efficacy of CYP2D6 substrates taken by Mexican Americans.

Adult↗
PubMed2005

Evolution of the DRD2 gene haplotype and its association with alcoholism in Mexican Americans.

The human D2 dopamine receptor gene (DRD2) plays a central role in the neuromodulation of appetitive behaviors and is implicated in having a possible role in susceptibility to alcoholism. We genotyped an SNP in DRD2 Exon 8 in 251 nonalcoholic, unrelated, healthy controls and 200 alcoholic Mexican Americans. The DRD2 haplotypes were analyzed using the Exon 8 genotype in combination with five other SNP genotypes, which were obtained from our previous study. The ancestral origins of the DRD2 polymorphisms have been determined by sequencing the homologous region in other higher primates. Twenty DRD2 haplotypes, defined as H1 to H20 based on their frequency from high to low, were obtained in this major minority population. The ancestral haplotype "I-B2-G-C-G-A1" and two one-step mutation haplotypes were absent in our study population. The haplotype H1, "I-B1-T-C-A-A1", with the highest frequency in the population, is a three-step mutation from the ancestral form. The first five or eight major haplotypes make up 87% or 95% of the entire population, respectively. The prevalence of the haplotype H1+ (H1/H1 and H1/Hn genotypes) is significantly higher in alcoholics and alcoholic subgroups, including early onset drinkers and benders, than in their respective control groups. The Promoter -141C allele is in linkage disequilibrium (LD) with five other loci in the nonalcoholic group, but not in the alcoholic group. All of the other five loci are in LD in both the alcoholic and control groups. The DRD2 TaqI B allele is in complete LD with the allele located in intron 6. Five SNPs, Promoter -141C, TaqI B (or Intron 6), Exon 7, Exon 8, and TaqI A, are sufficient to define the DRD2 haplotypes in Mexican Americans. Our data indicate that the DRD2 haplotypes are associated with alcoholism in Mexican Americans.

Adult↗
PubMed2004

Evolution of the tandem repeats in thymidylate synthase enhancer region (TSER) in primates.

The upstream regulatory region of the human thymidylate synthase gene (thymidylate synthase enhancer region, TSER) is length polymorphic, attributable to variable numbers of tandemly repeated copies of a 28-bp fragment. It has been found that TSER length polymorphism is correlated to malignancy risk. To further our understanding of the origin and evolution of TSER, this region was investigated among different primates, including hominoids, two subfamilies of the Old World monkeys (OWMs): colobines and cercopithecines, and two species of the New World monkeys (NWMs). In addition to humans, our results show that length polymorphism in TSER is also present in some primate populations, although it appears that this region is length monomorphic in many other primates. We identified three unique repeat motifs in TSER and defined them as R1, R2, and R3, respectively, starting from the 3' end. The same repeat motifs from different species are more similar to each other than different repeat motifs within same species are. Such a paraphyletic pattern suggests that divergence of the three repeat motifs predated divergence of the OWMs/hominoids and the NWMs. The most recent common ancestor (MRCA) of hominoids and the OWMs probably possessed triple repeats but now double and triple repeats are two dominant types in hominoids and the OWMs. In addition, our results show that each of the three repeat motifs may be lost independently. We have also found clues that recombination was involved in formation of tandem repeat polymorphism in TSER.

Alleles↗
PubMed2004

ADH1B*1, ADH1C*2, DRD2 (-141C Ins), and 5-HTTLPR are associated with alcoholism in Mexican American men living in Los Angeles.

BACKGROUND: The aim of the present study was to use a candidate gene approach to identify the genetic risk factors for alcoholism in Mexican Americans residing in the Los Angeles area. The genes selected include alcohol metabolizing genes and neurotransmitter genes, which have been shown in the literature to be associated with alcoholism in other ethnic groups. METHODS: Thirteen allelic variants from seven genes were evaluated for their role in alcoholism using alcoholic (n = 200) and nonalcoholic (n = 251) Mexican Americans. Those polymorphic sites include alcohol dehydrogenase (ADH1B, ADH1C), aldehyde dehydrogenase (ALDH2), cytochrome P-450 2E1 (CYP2E1) TaqI, DraI, RsaI, dopamine D2 receptor (DRD2) TaqI A, B, intron 6, exon 7, -141C Ins/Del, serotonin transporter (5-HTTLPR), and GABAA receptor beta3 subunit (GABRbeta3). RESULTS: The results demonstrate that Mexican Americans have extremely low allele frequency for both ALDH2*2 and ADH1B*2 and a relatively high frequency of ADH1C*2 and CYP2E1 c2 alleles. ADH1B*1, ADH1C*2, DRD2 (-141C Ins), and 5-HTTLPR were associated with alcoholism in Mexican Americans (p < 0.05). DRD2 Ins was associated with alcoholism in those alcoholics who carried the ADH1B*2 or ADH1C*1 protective alleles (p = 0.032 in genotype level and p = 0.015 in allele level). DRD2 TaqI A and B alleles were associated with early age of onset for drinking (p = 0.016 for TaqI A1 and p = 0.049 for TaqI B1 allele). CONCLUSIONS: Together, the data reveal unique genetic patterns in Mexican Americans that may be in part responsible for the heightened risk for alcoholism and alcohol-associated health problems in this population.

Adult↗
PubMed2004

Polymorphisms of CYP2C19 and CYP2D6 in Israeli ethnic groups.

BACKGROUND: The cytochrome P450 isoenzymes CYP2C19 and CYP2D6 catalyze reactions involved in the metabolism of many widely used drugs. Their polymorphisms give rise to important interindividual and interethnic variability in the metabolism and disposition of several therapeutic agents and may cause differences in clinical response to some drugs. Individuals who carry two null alleles of either gene are known as poor metabolizers (PMs), while those who carry more than two copies of the functional CYP2D6 gene are ultrarapid metabolizers (UMs). AIM: The aim of the current study was to genotype Israelis from four different ethnic backgrounds with respect to CYP2C19 and CYP2D6. STUDY DESIGN: Polymorphisms of the CYP2C19 and CYP2D6 genes were determined by genotyping the four ethnic groups using PCR and/or restriction fragment length polymorphism (RFLP) analysis. The groups consisted of three Jewish communities, Yemenite Jews (n = 36), Sephardic Jews (n = 47), Ethiopian Jews (n = 28), and one Arabian population, Bedouins (n = 50). RESULTS: CYP2C19*2 allele frequencies ranged from 12.0 to 19.6% among the four ethnic groups. Within the study population, the CYP2C19*3 gene was only found in one Bedouin individual, in the heterozygous state (CYP2C19*1/*3). In each group, one individual was homozygous for CYP2C19*2, and were predicted to be PMs. The data revealed a high prevalence of CYP2D6*2, *4, *10, *41, and gene duplication, followed by *5 and *17, while *3 was very rare. The frequencies of the CYP2D6*4, *10, and *17 alleles and CYP2D6 gene duplication were significantly different among the four groups. However, the CYP2D6*2, *3, and *5 and *41 alleles showed similar frequencies in the four groups. Four (8.5%) Sephardic Jews and one (2.0%) Bedouin were found with the genotype CYP2D6*4/*4 (two null alleles), and were thus presumably PMs. A total of 15 individuals, distributed in all groups, were found with functional CYP2D6 gene duplications. The frequencies of predicted UMs (duplication of CYP2D6) were 17.8% (5/28) and 12.8% (6/47) in Ethiopian Jews and Sephardic Jews, respectively, which were higher than that of Yemenite Jews (5.6%, 2/36) and Bedouins (4.0%, 2/50). CONCLUSIONS: This is the first study of the CYP2D6 gene polymorphism in Israeli ethnic groups, either Jewish or Arab. Furthermore, this is also the first study of the CYP2C19 gene polymorphism in Jewish or Arab subgroups living in Israel. The frequencies of various alleles for the CYP2D6 gene are significantly different among the ethnic groups in Israel. These new findings may have important clinical implications in administrating drugs metabolized by CYP2D6 and for CYP2D6-related adverse drug reactions in the Israeli population.

Alleles↗
PubMed2004

[Detection and typing for swine leukocyte antigen].

Traditionally the cluster of swine leukocyte antigen (SLA) was typed by serological, cytological and biochemical methods. Many special molecular typing methods have been developed with the progress of molecular biological technology, such as PCR-RFLP, PCR-SSCP , MS and DNA sequencing. Here we discussed the advantages and disadvantages of each method based on the polymorphic and conservative (from the functional aspect, such as supertype and supermotif) characteristics of SLA, and illustrated the development of typing for SLA in the future. In addition, we pointed out the editorial mistakes about the serological haplotype of SLA in reference book and emphasized that the accurate polymorphism of SLA-DQB gene must be based on the cloning sequencing.

Animals↗
PubMed2004

[Aldehyde dehydrogenase (ALDH2) polymorphism and drinking behavior].

An atypical allele (ALDH2*2) in low K(m) aldehyde dehydrogenase (ALDH2), which is highly prevalent in Asians, may influence drinking behavior because of higher production of acetaldehyde in the liver. High alcohol sensitivity such as flushing after drinking has been shown to be mainly due to the atypical ALDH2 genotypes. The atypical allele is associated with alcohol-induced liver injury and some cancers. Recently, the researches on the polymorphisms not only in the gene itself but also its frequencies in different Asian populations have been made great progress. Three factors, including different sex, age and geography, were also analyzed with the genotypes of ALDH2 in Chinese populations.

Alcohol Drinking↗
PubMed2002

Length polymorphism of thymidylate synthase regulatory region in Chinese populations and evolution of the novel alleles.

The tandemly repeated 28-bp sequence in the 5'-terminal regulatory region of human thymidylate synthase (TSER), which has been reported to be polymorphic in different populations, was surveyed in 668 Chinese from 9 Han groups, 8 ethnic populations, and 36 individuals representing a three-generation pedigree. Amplified fragments were separated by electrophoresis on 4% agarose gel. In addition to the reported double and triple repeats of the 28-bp sequence in TSER, we also detected a novel quintuple repeat in this region. The transient expression activity of TSER with the quintuple repeat is almost the same as that of the reported TSER with the triple repeat. All three alleles of the repeat type (2, 3, and 5) were further confined by sequencing. The frequencies of the TSER allele 2 and 3 were 18.82 and 81% in totally unrelated Chinese samples, respectively, while the frequency of allele 3 was variable in different Chinese populations with a range from 62 to 95%. On the basis of the sequences of the different alleles, the existence of the tandem repeats in each allele might be explained by slipped-strand mispairing during DNA replication.

Alleles↗