Related knowledge and background
Previous studies have demonstrated that the metabolic phenotype of (S)-mephenytoin 4’-hydroxylase (S-MP) is genetic polymorphism and involved in metabolisms of many drugs, such as mephenytoin, diazepam, phenobarbital, propranolol, omeprazole, proguanil, and pantoprazole[3]. Wrighton et al[8] isolated a new enzyme from human livers and named CYP2C19 in 1993. The hydroxylation metabolism of S-MP is mainly mediated by CYP2C19 protein.
Studies showed that, most of individual can perform hydroxylation metabolism of S-MP quickly, called extensive metabolizer, and a person who metabolizes a probe drug–the rate of which is related to the metabolizing cytochrome P-450 enzyme–slower than others was called poor metabolizer. It is eliminated primarily by oxidative metabolism through the CYP2C19 enzymatic pathway, namely, CYP2C19 genetic polymorphism. de Morais et al[4] found that two allelic mutable site of S-MP in Japanese poor metabolizers in 1994, which named CYP2C19m1 (exon 5 mutation) and CYP2C19m2 (exon 4 mutation). CYP2C19m1 and CYP2C19m2 are two independent alleles, the end product of which lack of catalytic activity, thus, it loss ability of hydroxylation metabolism to MP and other matters.
Kubota et al [9] demonstrated that, the frequency of CYP2C19 poor metabolizers of Oriental population (13%-23%) was obviously higher than that of Caucasians (3%-5%), in Japanese, the frequency was 18.86%, and which of the Black people lies between Caucasians and Oriental population. Accordingly, it is important to study the relationship between CYP2C19 genetic polymorphism and pharmacokinetics of Oriental population.
Results analysis
Most of the population of Xinjiang Uygur Autonomous Region is Uigur population, which different from Han population in history, culture and living habits. The results demonstrated that, the frequency of poor metabolizers of Uigur was lower than that of Han population, but the extensive metabolizers were higher than Han population. Allele frequency wt of Uigur was obviously lower than Han population, the m1 was 58-fold of m2, which was higher than Han population, but the m2 frequency was lower than Han population. It can be seen that the distribution features of CYP2C19 and m1 allele frequency in Uigur were similar to Caucasians. However, wt allele frequency was higher than Caucasians. The main gene mutation of CYP2C19 was m1, which was the same as Han population, but there was great difference in genetic polymorphism. The experiments also showed that, the phenotypic frequency of heterozygote (96.05%) was notably higher than that of homozygote (6.17%). Area features and certain acquired predisposition, such as eating habit, smoking or taking other drugs may be involved in this change besides varied history, culture and living habits[10-11].
Bias or deficiency of this study
The case number was small in this study, thus, the results should be verified by multi-center research with larger samples. This is also the focus of further study.
Clinical application significance
Pharamcogenomics is a hot focus at present. This paper explores the polymorphism distribution of CYP2C19 in Uigur population and obtains a different outcome compared with Han population. Ethnic difference is noted in CYP2C19 gene. Thus, it provides reference for analyzing distribution features of CYP2C19 gene variation.
Summary
The results revealed that, distribution frequency m1/m1 of poor metabolizers in Uigur population is obviously lower than that in Han population, and m1 frequency is higher than that of Han population, accordingly, m1 is the main gene variation of cytochrome P450 2C19 in Uigur population.
