Prevalence of CYP2C19 polymorphisms in the Lebanese population

Abstract

Clopidogrel is one of the most commonly prescribed drugs, as its combination with low-dose aspirin is the recommended oral anti-platelet therapy, to prevent ischaemic events following coronary syndromes or stent placement. Numerous recent studies have shown that polymorphisms in the gene encoding the cytochrome P450 (CYP450) 2C19 enzyme (CYP2C19) contribute to variability in response to clopidogrel; patients with certain common genetic variants of CYP2C19 (2, 3) have a reduced metabolism of clopidogrel and have a higher rate of cardiovascular events or stent thrombosis compared to patients with the CYP2C19 (1) allele. CYP2C19 2 is most common in Caucasians, Africans and Asians while CYP2C19 3 has been found mostly in Asians. Since the prevalence of these variants in the Lebanese population has not yet been reported, our aim was to determine the genotypes of CYP2C19 in our population. CYP2C19 (1/2/3) variants were assessed by Polymerase Chain Reaction-Restriction Length Polymorphism (PCR-RFLP) assays in a representative sample of 161 unrelated healthy Lebanese volunteers. The allele frequencies of CYP2C19 2 and 3 were 0.13 and 0.03. Carriers of the CYP2C19 2 or 3 represented 24.2% of the subjects. Our data show no significant difference in the frequency of CYP2C19 allelic variants when compared to Caucasian populations and demonstrate that the application of the recent FDA recommendations would also be beneficial in Lebanon, allowing physicians to identify patients at high risk for atherothrombotic events, and eventually advising them to consider other antiplatelet medications or alternative dosing strategies in poor metabolizers.

Genotype-Phenotype Analysis of CYP2C19 in Healthy Saudi Individuals and its Potential Clinical Implication in Drug Therapy

“…For example, a similar distribution was found in Romanian (13.7%), Danish (15.0%), German (15.2%), Russian (11.4%), Italian (11.9%), and Portuguese ethnic groups (13.0%) 21, 22, 23, 24, 25, 26. In addition, we did not find any significant differences (p >0.05) in the CYP2C19*2 allele frequency when comparing our population with other Middle East ethnicities such as Iranian (14% ), Israeli (15%), Turkish (12%), Lebanese (13%) and Egyptian people (10.9%) 29,30,31,32,33. In East and South Asian groups (Chinese, Japanese, Koreans and Thai), the CYP2C19*2 allele frequencies (range: 24.9%-29.0%) were significantly higher than seen in the Saudi Arabian population (p<0.05) 34, 35, 36, 37, 38.…”

ABCB1 C3435T and CYP2C19*2 polymorphisms in a Palestinian and Turkish population: A pharmacogenetic perspective to clopidogrel

“…Palestinians and Turkish populations showed similarities in CYP2C19*2 allele frequency with some of other populations in the Middle East ( Djaffar Jureidini et al, 2011 , Hamdy et al, 2002 , Yousef et al, 2012 ). The homozygous mutant genotype of CYP2C19*2 (*2/*2) was not detected in neither the Palestinian population sample nor the Turkish sample while other studies reported the presence of this genotype in their population samples ( Akhlaghi et al, 2011 , Aynacioglu et al, 1999 , Sameer et al, 2009 , Zalloum et al, 2012 ).…”

(Frequency of CYP2C19 Gene Polymorphisms (SNP) and its Impact on Clinical Outcome in Ischemic Heart Disease Patients Taking Clopidogrel after percutaneous coronary intervention (PCI

“…The importance of this study related to fact that an understanding of distribution of SNPs is crucial for the future application of pharmacogenomics to different population groups. Such applications have recently been performed in warfare in therapy (31) in our study, the frequency of CYP2C19 *1, *2 and *3, *17 was 48%, 17%, 1%, 34% respectively, allelic frequency of CYP2C19*2 is higher than reported in Iraqi population 15.2%) (32) , Saudi Arabia(15%) (33) , Jordanian(16%) (34) , Lebanese (13.4%) (35) , Tunisian region (11.5%) (36) . German (15.2%) (37), Belgian(9.1%) (38) Ethiopians (14%) (39) , and lower than reported in Japanese (27.4%) (40) , Chinese (45.5%) (41) , Koreans(20.9%) (42) .…”