Distribution of the Major Cytochrome P450 (CYP) 2C9 Genetic Variants in a Saudi Population

Abstract

Cytochrome P450 (CYP) 2C9 is responsible for the metabolism of a number of widely used drugs such as oral anticoagulants, oral antidiabetics and non-steroidal anti-inflammatory drugs. The CYP2C9 is a genetically polymorphic enzyme. The most common allele is CYP2C9*1, while CYP2C9*2 and CYP2C9*3 are the less-frequent variants. The activity of the enzyme encoded by either CYP2C9 *2 or *3 variant is lower compared with that of the CYP2C9*1. The metabolism of most of the CYP2C9 substrates decreases in varying degrees in subjects carrying the CYP2C9 *2 or *3 allele. The aim of this study was to investigate the frequencies of the major variants of the CYP2C9 in Saudi Arabians.

In vitroassessment of 39CYP2C9variants found in the Chinese population on the metabolism of the model substrate fluoxetine and a summary of their effects on other substrates

“…5,22,23 There is considerable evidence of significant differences between various racial and ethnic populations in both the frequency and types of CYP2C9 polymorphisms. [24][25][26] Two dominant variants, CYP2C9*2 and CYP2C9*3, are common in Caucasians at frequencies of approximately 11% and 7%, respectively, whereas significantly lower frequencies of these variants are found in African and Asian populations. 12,14 In European populations, a large-scale genetic polymorphism study revealed that approximately 40% of individuals carry these two mutated alleles.…”

Genotyping ofCYP2C9andVKORC1in the Arabic Population of Al-Ahsa, Saudi Arabia

“…Among Arabs in general, there exists great intraethnic variability in the frequencies of the CYP2C9 *2 and *3 alleles. In Saudi Arabia, Mirghani et al [14] reported that the frequencies of the CYP2C9 *2 and *3 alleles among Saudis residing in Riyadh were similar to those in Caucasian populations (11.7% and 9.1%, resp.) [14].…”

“…In Saudi Arabia, Mirghani et al [14] reported that the frequencies of the CYP2C9 *2 and *3 alleles among Saudis residing in Riyadh were similar to those in Caucasian populations (11.7% and 9.1%, resp.) [14]. Unpredictably, the frequency of CYP2C9 *3 was significantly different from the frequency of *3 in our study group (Table 3).…”

“…Furthermore, the frequency of the CYP2C9 *3 allele is significantly lower in Asian populations (as low as 3.3%, compared to 4%–16% in Caucasians) [5, 13]. In Arabian populations, intraethnic variability in the frequency of the CYP2C9 *2 and *3 alleles has been reported, ranging from 7% to 21% and 3% to 9%, respectively [14–18]. In the case of the VKORC1 –1639G>A polymorphism, interethnic variability in –1639AA frequency has also been reported [19].…”

Individualized medicine enabled by genomics in Saudi Arabia

“…CYP2C subfamily of enzymes metabolizes about 20% of clinically relevant drugs including non-steroidal anti-inflammatory drugs (NSAIDs), oral anticoagulants and oral anti-diabetic agents such as tolbutamide, glibenclamide, glimepiride and glipizide [ 141 - 143 ]. To date, more than 57 alleles of CYP2C9 have been reported [ 144 ] amongst which CYP2C9*2 and CYP2C9*3 alleles are the most prevalent in Caucasian as well as Asian populations and individuals carrying these polymorphisms exhibit reduced CYP2C9 activity [ 141 ].…”