Variants of the Solute Carrier SLC16A1 Gene (MCT1) Associated With Metabolic Responses During a Long-Graded Test in Road Cyclists.

Variants of the solute carrier SLC16A1 gene have been associated with alterations in MCT1 expression, because of a lactate (La) transport deficiency across the cell membrane and a blood La accumulation. The aim of this study was to associate the allelic and genotypic frequencies of 1470T>A, 2917(1414) C>T, and IVS3-17A>C variants relative to the blood La kinetics and metabolic responses to a progressive effort until exhaustion. Twenty-five well-trained road cyclists performed a long-graded laboratory test: 10 minutes at 2.

Genetic polymorphisms of CYP2C8, CYP2C9 and CYP2C19 in Ecuadorian Mestizo and Spaniard populations: a comparative study.

This study was designed to investigate the potential differences between Spaniards and Ecuadorian Mestizo people regarding CYP2C8, CYP2C9, and CYP2C19 genetic polymorphisms. DNA from 282 Spaniard and 297 Ecuadorian subjects were analyzed by either a previously reported pyrosequencing method (CY2C8*3, CYP2C9*2, CYP2C9*3, CYP2C19*2 and CYP2C19*3) or a nested PCR technique (CYP2C19*17). Whereas CYP2C19*17 allele distribution was higher in Ecuadorians than in Spaniards (P < 0.

Toward a clinical practice guide in pharmacogenomics testing for functional polymorphisms of drug-metabolizing enzymes. Gene/drug pairs and barriers perceived in Spain.

The development of clinical practice recommendations or guidelines for the clinical use of biomarkers is an issue of great importance with regard to adverse drug reactions. The potential of pharmacogenomic biomarkers has been extensively investigated in recent years. However, several barriers to implementing the use of pharmacogenomics testing exist.

Differences between Spaniards and Ecuadorians in CYP2A6 allele frequencies: comparison with other populations.

This study was designed to investigate the potential differences between Spaniards and Ecuadorian Mestizo people regarding CYP2A6*1A, CYP2A6*1B1, CYP2A6*1x2A, CYP2A6*9A, and CYP2A6*4A variant alleles at the CYP2A6 gene and also to compare the observed frequencies with those previously reported in different ethnic groups. DNA from 234 Spaniard and 300 Ecuadorian subjects were analyzed by either PCR or PCR-restriction fragment length polymorphism. Differences between Spaniards and Mestizo Ecuadorians were detected in relation to the frequencies of the alleles linked to either absent enzyme activity, CYP2A6*4A (4 and 7.

Haplotype structure and allele frequencies of CYP2B6 in Spaniards and Central Americans.

This study was aimed to investigate the potential differences in allele frequencies of the CYP2B6 gene between Spaniards and Central Americans. Three single nucleotide polymorphisms of the CYP2B6 gene 516 G>T, 785 A>G and 1459 C>T were assayed by a polymerase chain reaction in 180 Spaniards and 182 Central Americans. The allele frequencies for CYP2B6*1, CYP2B6*4, CYP2B6*5, CYP2B6*6, CYP2B6*9 in Spaniards and Central Americans were 0.

CYP3A5 3, CYP3A4 1B and MDR1 C3435T genotype distributions in Ecuadorians.

Polymorphisms in CYP3A genes, such as CYP3A5} and CYP3A4, as well as in the MDR1 gene, which encodes for P-glycoprotein, have been implicated as genetic markers in several disorders. Differences in the frequency distribution of the allelic variants CYP3A5 3, CYP3A4 1B, and MDR1 3435T have been demonstrated between distinct ethnic groups. In this study we examined the frequency of these allelic variants in 317 healthy Mestizo individuals from Ecuador and made comparisons with results reported in the literature.

Growth hormone does not alter CYP2A6 activity in growth hormone-deficient children.

A large number of metabolic alterations are increasingly being treated with growth hormone. Despite the fact that growth hormone is known to be the main regulator of several hepatic drug metabolizing enzymes in rodents, few studies deal with the effect of growth hormone on hepatic enzyme activities in human beings. The aim of this study was to determine the effects of growth hormone replacement therapy for 4 weeks on CYP2A6 activity in children, because changes in this enzyme activity may have important therapeutic and toxic consequences.

CYP3A5*3 and CYP3A4*1B allele distribution and genotype combinations: differences between Spaniards and Central Americans.

The aim of this study was to detect genotypic differences between three populations of healthy volunteers from Northern Spain (204 subjects), Nicaragua (120 subjects), and El Salvador (112 subjects) regarding CYP3A4*1B and CYP3A5*3 polymorphisms. No significant differences were found by comparing allelic frequencies between the two Central American populations. The CYP3A5*3 allele frequency was significantly different (P < 0.

Polymorphism C3435T of the MDR1 gene in Central Americans and Spaniards.

The human multidrug resistance gene (MDR1) encodes for P-glycoprotein (P-gp) which is a transmembrane transporter protein that acts as an efflux pump for a number of lypophilic compounds. It plays a protective role for cells against DNA damage. The wobble C3435T polymorphism at exon 26 has been associated with different expression levels and activity.

Lack of effect of growth hormone replacement therapy on CYP1A2 and xanthine oxidase activities in growth hormone-deficient children.

Background And Objectives: The recombinant human growth hormone (rhGH) is being increasingly used for a number of metabolic alterations. GH is the main regulator of several hepatic drug metabolizing enzymes in rodents. In addition, GH could play a major role in defining the interface between pharmacogenetics and development.

Urinary mutagenicity, CYP1A2 and NAT2 activity in textile industry workers.

The two major causes of bladder cancer have been recognised to be cigarette smoke and occupational exposure to arylamines. These compounds are present both in tobacco smoke and in the dyes used in textile production. Aromatic amines suffer oxidative metabolism via P450 cytochrome CYP1A2, and detoxification by the polymorphic NAT2.

Effects of growth hormone deficiency and rhGH replacement therapy on the 6beta-hydroxycortisol/free cortisol ratio, a marker of CYP3A activity, in growth hormone-deficient children.

Objective: To determine the effect of both growth hormone deficiency (GHD) and rhGH replacement therapy on CYP3A activity as well as the potential influence of gender.

Methods: The sample consisted of 35 GHD children (16 males and 19 females), aged 2.9-13.

Omeprazole treatment: genotoxicity biomarkers, and potential to induce CYP1A2 activity in humans.

Omeprazole is one of the most used acid-suppressing medications. This fact emphasizes the questions concerning the safety of this compound. Healthy volunteers (n=33) were included in this prospective study.

Frequency distribution of C3435T mutation in exon 26 of the MDR1 gene in a Spanish population.

P-glycoprotein (PGP) is a transmembrane efflux transporter with an important role in drug therapy. The level of PGP expression leads to relevant consequences in terms of efficacy and toxicity by modulating drug disposition. A single nucleotide polymorphism (SNP) in exon 26 of the gene C3435T was recently associated to PGP levels and substrate uptake.

Influence of the urine flow rate on some caffeine metabolite ratios used to assess CYP1A2 activity.

Five established metabolite ratios (MRs) to measure P450 CYP1A2 activity--MR1 (17X + 17U)/137X, MR2 (AFMU + 1X + 1U)/17U, MR3 (17X/137X), MR4 (AFMU + 1X + 1U + 17X + 17U)/137X, and MR5 (AFMU + 1X + 1U)/17X--were calculated in urine 4-5 hours after caffeine intake. First, to assess the potential of omeprazole to induce CYP1A2 activity, a caffeine test was performed in 27 subjects on two occasions: before and after 14 days on omeprazole (20 mg/day). Samples of urine were analyzed by high-performance liquid chromatography (HPLC) to quantify caffeine and metabolites used to calculate the different caffeine MRs.

Characterization of a novel CYP2A7/CYP2A6 hybrid allele (CYP2A6*12) that causes reduced CYP2A6 activity.

The human CYP2A6 enzyme metabolizes certain drugs and pre-carcinogens and appears to be the most important enzyme for nicotine metabolism. At present, more than 10 different allelic variants are known that cause abolished or decreased enzyme activity. Genetic polymorphism in this gene might be of particular importance for an individual's need for nicotine and for susceptibility to lung and/or liver cancer.