Global Pharmacogenetics: Genetic Substructure of Eurasian Populations and its Effect on Variants of Drug-Metabolizing Enzymes

Makeeva, O. A.; Степанов, В. Г.; Puzyrev, V. P.; Goldstein, David B.; Grossman, Iris

doi:10.2217/14622416.9.7.847

Cited by 35 publications

(35 citation statements)

References 70 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, compared with the CYP2E1*6 allele frequency in the Caucasian population (11.4%), significant differences were observed in the mainland Chinese Han (26.2%, Po0.01) and Chinese Uygur (18.8%, Po0.05) populations, but no significant difference was observed in the Chinese Kazakh population (14.5%), leading to speculation that this discrepancy might be due to the ethnic complexity of this Eurasian admixed population. The present results support the proposition that the P450 genetic distances were well correlated with the geographic distances across Eurasian populations, 17 and indicate potential relevance to clinical decision making.…”

Section: Resultssupporting

confidence: 87%

Frequencies of genotypes and alleles of the functional SNPs in CYP2C19 and CYP2E1 in mainland Chinese Kazakh, Uygur and Han populations

Wang¹,

Zhu

Li³

et al. 2009

J Hum Genet

View full text Add to dashboard Cite

CYP2C19 and CYP2E1 show great genetic differences between Orientals and Caucasians. The objective of this study was to investigate the genotype and allele distribution patterns of CYP2C19 and CYP2E1 polymorphisms among healthy participants in mainland Chinese Kazakh, Uygur and Han populations by the PCR-restriction fragment length polymorphism technique. The allele frequencies of CYP2C19*2, CYP2E1*5B and CYP2E1*6 were significantly lower in the Chinese Kazakh (15.4, 11.2 and 14.5%, respectively) (Po0.05) and Uygur (16.1, 12.1 and 18.8%) (Po0.05) populations than that in the Chinese Han population (28.8, 19.4 and 26.2%), but the frequencies of CYP2C19*3 were similar among the three populations (8.0, 9.4 and 7.2%). Frequencies of the three combined genotypes, one for predicted CYP2C19 poor metabolizers and two for predicted high levels of CYP2E1 transcription, were significantly lower in the Chinese Kazakh (7.5, 19.6 and 28.0%, respectively) (Po0.05, v 2 -test) and Uygur (8.1, 22.8 and 33.6%) (Po0.05) populations compared with the Chinese Han population (16.5, 35.9 and 44.7%). The present research shows that frequencies of the functional single-nucleotide polymorphisms in the CYP2C19 and CYP2E1 genes vary in the Chinese Kazakh, Uygur and Han populations, suggesting that disease susceptibilities or drug responses associated with enzyme activities of CYP2C19 and CYP2E1 may differ in the diverse ethnic populations in mainland China.

show abstract

Section: Resultssupporting

confidence: 87%

Frequencies of genotypes and alleles of the functional SNPs in CYP2C19 and CYP2E1 in mainland Chinese Kazakh, Uygur and Han populations

Wang¹,

Zhu

Li³

et al. 2009

J Hum Genet

View full text Add to dashboard Cite

show abstract

“…Most Caucasians expressed the CYP3A5 6986GG genotype associated with a small amount of translated CYP3A5 protein, with a G allele frequency ranging from 0.87 to 0.94 in various Caucasian populations (22,29). In contrast, in various Asian populations, G allele frequencies were lower, ranging from 0.59 in Indians to 0.65 in Cambodians, as demonstrated in this study, 0.67 in a Vietnamese population, and 0.74 to 0.78 in Japanese, Chinese, and Korean populations (23,29). The frequency is even lower in patients of African descent (0.36) (22).…”

Section: Discussionmentioning

confidence: 99%

Population Pharmacokinetic-Pharmacogenetic Study of Nevirapine in HIV-Infected Cambodian Patients

Chou

Bertrand

Ségéral

et al. 2010

Antimicrob Agents Chemother

View full text Add to dashboard Cite

The aims of this ANRS12154 open-label, single-center, multiple-dose pharmacokinetic study were to characterize nevirapine pharmacokinetics in a Cambodian population of HIV-infected patients and to identify environmental and genetic factors of variability, focusing on the CYP2B6, CYP3A5, and ABCB1 (MDR1) genes. A total of 170 Cambodian HIV-infected patients were included. Nevirapine trough concentrations were measured after 18 and 36 months of starting antiretroviral treatment and in samples drawn during a dosing interval in a subset of 10 patients. All data were analyzed by nonlinear mixed-effects modeling. The effect of covariates was investigated using the population pharmacokinetic model. Patients carrying homozygous lossof-function alleles CYP3A5 6986A>G, CYP2B6 516G>T, CYP2B6 1459C>T, and ABCB1 3435C>T represent 42.4%, 9.2%, 0%, and 18% of the population, respectively. The median nevirapine trough concentrations did not differ after 18 and 36 months of treatment (5,705 ng/ml [range, <50 to 13,871] and 5,709 ng/ml [range, <50 to 15,422], respectively). Interpatient and intrapatient variabilities of nevirapine apparent clearance were 28% and 17%, respectively. CYP2B6 516G>T and creatinine clearance were found to significantly affect nevirapine apparent clearance. The estimated nevirapine apparent clearances were 2.95 liters/h, 2.62 liters/h, and 1.86 liters/h for CYP2B6 516GG, CYP2B6 516GT, and CYP2B6 516TT genotypes, respectively. The impact of creatinine clearance was small. This study demonstrates that 95% of the patients had sustained nevirapine exposure well above the 3,000-ng/ml threshold. Nevirapine clearance was shown to be affected by CYP2B6 516G>T genetic polymorphism and creatinine clearance, although this explained only part of the interpatient variability, which remains low compared to that for other antiretroviral drugs.In resource-limited settings, nonnucleoside HIV-1 reverse transcriptase inhibitors (NNRTI) are the WHO-recommended backbone of first-line antiretroviral therapy. At the time of the study, nevirapine in combination with two nucleoside analog inhibitors of reverse transcriptase such as stavudine and zidovudine, in addition to lamivudine, was the recommended antiretroviral regimen in treatment-naïve patients, mainly because of the availability of WHO-prequalified low-cost generic fixed-dose combinations (7, 27). In Cambodia, the prevalence of HIV infection among the general population aged between 15 and 49 years peaked at 2% in 1998 and declined to 0.9% in 2006. This decrease has been attributed to many deaths among people infected during the early years of the epidemic before implementation of the continuum of care and the scaling-up of HIV prevention, care, and treatment programs. At the end of 2009, it is estimated that about 37,000 patients were on antiretroviral drug regimens and 69.5% were on a nevirapine backbone regimen (National Center for HIV/AIDS, Dermatology and STD [NCHADS]; http://www.nchads.org/). Therefore, worldwide, most patients living with AIDS who need antiretr...

show abstract

“…The frequencies of defective CYP2C9 alleles (CYP2C9*2 and CYP2C9*3) are higher in Caucasians (18.9%) than in Asians (2.5-3.5%) [11,12]. Conversely, the frequencies of defective CYP2C19 alleles (CYP2C19*2 and CYP2C19*3) are higher in Asians (33-43.5%) compared to Caucasians (13.6%) [11][12][13]. Population studies have shown that individuals can be classified into three subgroups: namely, homozygous extensive metabolizers (homo EMs), heterozygous EMs (hetero EMs) and poor metabolizers (PMs) according to the number (i.e.…”

Section: Cyp Polymorphisms and Aed Therapymentioning

confidence: 99%

The clinical impact of cytochrome P450 polymorphisms on anti-epileptic drug therapy

Saruwatari

Ishitsu

Shioiri

et al. 2010

E&S

View full text Add to dashboard Cite

Global Pharmacogenetics: Genetic Substructure of Eurasian Populations and its Effect on Variants of Drug-Metabolizing Enzymes

Abstract: Although the tested variants were present in the neighboring, yet secluded, populations at the expected range of frequencies, the observed frequencies were significantly variable across Eurasian populations, indicating potential relevance to clinical decision making.

Cited by 35 publications

References 70 publications

Frequencies of genotypes and alleles of the functional SNPs in CYP2C19 and CYP2E1 in mainland Chinese Kazakh, Uygur and Han populations

Frequencies of genotypes and alleles of the functional SNPs in CYP2C19 and CYP2E1 in mainland Chinese Kazakh, Uygur and Han populations

Population Pharmacokinetic-Pharmacogenetic Study of Nevirapine in HIV-Infected Cambodian Patients

The clinical impact of cytochrome P450 polymorphisms on anti-epileptic drug therapy

Contact Info

Product

Resources

About