Investigation of allele and genotype frequencies of CYP2C9, CYP2C19 and VKORC1 in Iran.
Journal Title: Pharmacological Reports - Year 2010, Vol 62, Issue 4
Abstract
Research has shown that there are significant ethnic variations in the frequency of highly functional mutations in genes coding for metabolic enzymes. However, few studies have examined the frequency distribution of major allelic variations within the population of Iran. The present study focused on the genotype profile of southern Iranians in order to compare the allelic frequencies of CYP2C9, CYP2C19, and VKORC1 -1639G>A (all of which have been shown to have significant roles in the metabolism of warfarin) with those of other populations. Therefore, genotyping was carried out on 150 subjects (50 healthy volunteers and 100 outpatient subjects) by polymerase chain reaction- restriction length polymorphism (PCR-RFLP). Findings indicated both similarities and differences in the distribution of polymorphic alleles of CYP2C9, CYP2C19 and VKORC1 between southern and northern Iranians. For example, the frequency of CYP2C9*3 among southern Iranians (9.8%) was found to be similar to the frequency found among Caucasians (in this case, Italians) (9.7%) but was higher than the frequency found among Africans (1%), Japanese (2.3%), and northern Iranians (0%). These findings confirmed significant inter-ethnic differences in CYP2C9 frequencies between southern and northern Iranians The reported frequency of CYP2C9*2 in our subjects (25.3%) was different from the frequencies seen in Caucasian (10-13%), African (2%) and Asian (0%) populations. The CYP2C19*2 and CYP2C19*3 allelic frequencies were similar to the Caucasian population. For VKORC1, the allelic frequency of -1639A (55.6%) was in accordance with Caucasian, but different from Chinese (96%) and African-American populations (13%). The findings confirmed some important interethnic differences in the metabolic capacity for drug clearance. Because the population of Iran consists of several ethnicities, this type of analysis can help explain the genetic diversity between the populations of northern and southern Iran. In addition, the results of this study will be useful for understanding clinical pharmacokinetics and drug dosage recommendations for Iranians.
Authors and Affiliations
Negar Azarpira, Soha Namazi, Fatemeh Hendijani, Maryam Banan, Masumeh Darai
Keywords
Related Articles
- EP ID EP144858
- DOI -
- Views 98
- Downloads 0
Nitric oxide modulation mediates the protective effect of trazodone in a mouse model of chronic fatigue syndrome.
The present study was conducted with the aim of elucidating the possible role of nitric oxide (NO) in the neuroprotective effects of trazodone used to treat chronic fatigue syndrome (CFS) in mice. Male albino mice were f...
Neonatal co-lesion by DSP-4 and 5,7-DHT produces adulthood behavioral sensitization to dopamine D(2) receptor agonists.
To assess the possible modulatory effects of noradrenergic and serotoninergic neurons on dopaminergic neuronal activity, the noradrenergic and serotoninergic neurotoxins DSP-4 N-(2-chlorethyl)-N-ethyl-2-bromobenzylamine...
Responsiveness of 5-HT(2C) receptors in repeatedly diazepam-injected rats: a behavioral and neurochemical study.
The role of 5-hydroxytryptamine (serotonin; 5-HT)(2C) receptors in anxiety and the anxiolytic effects of drugs is well documented. In view of the withdrawal anxiety associated with repeated diazepam intake, the present s...
Effect of HMG-CoA (3-hydroxy-3-methylglutaryl-CoA) reductase inhibitors on the concentration of insulin-like growth factor-1 (IGF-1) in hypercholesterolemic patients.
Studies have shown that HMG-CoA reductase inhibitors (statins) play an important role in the prevention and treatment of atherosclerosis and hyperlipidemia. The aim of this study was to investigate the effect of 3-month...
Commonly used ryanodine receptor activator, 4-chloro-m-cresol (4CmC), is also an inhibitor of SERCA Ca2+ pumps.
4-Chloro-m-cresol (4CmC) is an extensively used activator of ryanodine receptors (RyRs). Studies have shown that 4CmC, at a concentration of 1 mM, is sufficient to cause Ca(2+) release through RyRs. Here, we show that mM...