Personalized medicine is one of the highly advanced fields of medical sciences. This branch of science delves into the patient’s physiologic and pathophysiologic features and selects and carries out an appropriate and specific therapeutic approach for the patient [1]. Concentrating on the patient as the focal point rather than the disease augments the treatment effectiveness and decreases the probable side effects [2]. Despite the positive aspects of this system, achieving such an extent of knowledge of the patient’s features to implement personalized medicine necessitates a tremendous amount of detailed information about patient physiology and pathophysiology ^[3][4][3,4]. So far, there have been numerous studies regarding the matter at hand. Primarily, an effort has been made to genetically assess the specific populations, such as the people of a country, and compare them to other countries ^[5][6][7][6,7,8]. Following that, the ethnicities of various countries have been studied and compared ^[8][9][10][9,10,11]. Such assessments/studies greatly help access the required information and individualized therapies.

Cytochrome p450 (CYP450) is one of the most potent metabolizing enzymes in the body. It metabolizes many endogenic and exogenic substances ^[11][12][13][16,17,18]. Differences in genotype and phenotype alter the enzyme’s activity. Aside from intra-individual changes in these enzymes’ activity by several physiological, pathological, and environmental factors ^{[14][15][16][17][18][19][20]}[19,20,21,22,23,24,25], any change in the enzyme activity may alter pharmacotherapeutic efficiency and decrease or increase adverse drug reactions ^{[21][22][23][24]}[26,27,28,29]. Hence, in personalized medicine, the enzyme family is one of the parameters that increase the specificity of pharmacotherapy in patients under investigation. A genetic assessment of CYP450 enzymes reveals that they fall into four categories: poor, intermediate, extensive, and ultra-rapid metabolizers, which have low, moderate, usual, and high activity, respectively ^[25][30]. As previously stated, the patient’s response to therapy is not always consistent with his genotype. For instance, the patient’s genotype indicates that the CYP450 enzyme is normal, but the pharmacotherapy response indicates the enzyme’s decreased activity ^[26][31]. In such cases, it has been demonstrated that an enzyme’s activity and phenotype are not concordant with the corresponding genotype for various reasons, such as diseases, medication use, diet, and the like. This phenomenon is known as phenocoversion. Nonetheless, the primary assessment of personalized medicine begins with genotyping ^[27][28][32,33].

In recent years, several studies have been conducted on the genotype of some cytochrome 450 enzymes in the Iranian population. In these studies, one cytochrome was investigated in one group of patients or a specific ethnicity ^{[10][29][30][31]}[11,34,35,36]. However, no study has comprehensively investigated the important cytochromes P450 across various ethnicities in Iran’s population. Results revealed that, while there are some similarities, there are many genotype differences between the cytochrome P450 enzyme of the Iranian population and the other populations mentioned above ^[32][37]. These findings highlighted the importance of conducting additional individual studies on the Iranian population to gain more information. Such data can advance personalized medicine, improve pharmacotherapy efficiency, and reduce probable unintended adverse effects in Iranian patients (concerning the genetic profile of cytochrome P450 enzymes).

2. CYP1A2

A previous study demonstrated that the frequency of the *1 allele in the Iranian population was 39.8% ^[32][37]. The only SNP with a frequency greater than 1% in the Iranian population is the *1F allele, which has a frequency of 59.9%. The Persian (66.8%) and the Persian Gulf Islander (50%), among the eight Iranian ethnicities, have the highest and lowest frequency, respectively. There are no similarities in the frequency of the *1F allele between Iranian ethnicities and any other studied populations (Caucasian, European, Middle Eastern) (difference more significant than 1%) ^[33][34][35][44,47,55]. Additionally, genotypic analysis of these ethnicities revealed that the Kurds (51.5%) and the Persian Gulf Islanders (31.6%) have the highest and lowest frequency of homozygote genotype of CYP1A2*1F, respectively. In comparison, the Baloch (42.4%) and Kurds (28.8%) had the highest and lowest heterozygote genotype frequencies, respectively. In the Iranian population, the mean frequency of CYP1A2 homozygous and heterozygous genotypes based on the *1F allele were 41.5% and 36.6%, respectively.

3. CYP2B6

The *1 allele was found in 54.7% of the Iranian population ^[32][37]. The *9 allele had the highest prevalence (26.6%) in the Iranian population, ranging from 30.5% in the Lur to 24.0% in the Persian. The frequency of this allele among the Iranian Arabs was similar to the Caucasian race ^[36][66], the Persian similar to the European population, and the Lur to the Middle Eastern population ^[37][38][39][40,45,52]. Additionally, genotypic investigation of these ethnicities revealed that the Lur (9%) and Persian (5%) had the highest and lowest frequency of homozygote genotypes, respectively. In comparison, the Lur (43%) and the Persian (38%), respectively, had the highest and lowest frequency of heterozygote genotypes. In the Iranian population, the mean frequency of CYP2B6 homozygous and heterozygous genotypes based on the *9 allele were 6.2% and 40.6%. The *5 allele was the second most prevalent allele (8.5%) among the Iranian population, ranging from 10% in the Arab and Baloch to 6.5% in the Persian. This allele frequency among Arab and Baloch of the Iranian population was similar to the Caucasian race ^[36][66]. In contrast, none of the Iranian ethnicities were similar to the European population or the Middle Eastern population ^[37][38][39][40,45,52]. Furthermore, genotypic analysis of these ethnicities revealed that the Baloch (2%) had the highest frequency of homozygote genotype, while Turkmen, Lur, Far, and Persian Gulf Islander did not. On the other hand, among the Iranian population, Arab and Turkmen (18%) and Persian (13%) had the highest and lowest frequency of heterozygote genotype, respectively. The mean frequency of CYP2B6 homozygous and heterozygous genotypes based on the *5 allele were 0.6% and 15.7% in the Iranian population, respectively. Among Iranian ethnics, the *2 allele prevalence ranged from 8.5% in the Persian to 1.5% in the Turkmen. The frequency of the *2 allele among Baloch and Lur of the Iranian populations was similar to the Caucasian race and the European populations ^[36][66]. Moreover, the Arabs were similar to the Middle Eastern population in terms of the *2 allele frequency ^[37][38][39][40,45,52]. Additionally, a genotypic investigation of Iranian ethnics revealed that Fars, Arab, Kurd, and Baloch had a 1% frequency of homozygote genotype, whereas other ethnicities did not have this genotype. On the other hand, among the Iranian population, the Persian (15%) and the Turkmen (3%) had the highest and lowest frequency of heterozygote genotype, respectively. Mean frequency of CYP2B6 homozygous and heterozygous genotype based on the *2 allele was 0.5% and 9.6% in the Iranian population. The *22 allele had a 2.6% frequency in the Iranian population. It ranged from 4.5% among the Persians to 1% among the Persian Gulf Islanders. This allele’s frequency was similar to that of the Caucasian race, except for Persian and Persian Gulf Islanders ^[40][67]. Moreover, the frequency of this allele was similar to the European population of Kurd, Lur, and Persian Gulf Islanders. Furthermore, a genotypic investigation of these ethnicities revealed that the homozygote genotype was not found among any of the Iranian ethnicities. The Persian (95) and the Persian Gulf Islander (2%), on the other hand, had the highest and lowest frequency of heterozygote genotype among the Iranian population, respectively. In the Iranian population, the mean frequency of CYP2B6 homozygous and heterozygous genotypes based on the *9 allele was 0 and 5.2%, respectively. The *3 allele had the lowest prevalence (1.3%) in the Iranian population, ranging from 4% in the Persians to 0% in the Baloch. The frequency of this allele in the Azeri, Persian Gulf Islander, and Turkmen populations was similar to that of the Caucasian race and the European population ^[36][66]. Similar to the *22 allele, genotypic analysis of these ethnicities revealed that the homozygote genotype was not found among any Iranian ethnicity. On the other hand, the Persian race (8%) had the highest frequency of heterozygote genotype. In comparison, the Baloch showed no heterozygote genotype. In the Iranian population, the mean frequency of CYP2B6 homozygous and heterozygous genotypes based on the *3 allele was 0 and 2.6%, respectively.

4. CYP2C8

According to the previous study, the frequency of the *1 allele was 95% in the Iranian population ^[32][37]. The *4 allele prevalence ranged from 5.5% in the Kurds to 0.5% in the Persians among Iranian ethnicities. None of the Iranian ethnicities had a frequency of the *4 allele similar to the Caucasian race ^[41][68]. The frequency of this allele among the Kurds was similar to the European population. Moreover, Arab, Lur, and Turkmen populations were similar to the Middle Eastern population regarding the *4 allele frequency ^[42][50]. Additionally, a genotypic study of Iranian ethnicities revealed that only the Azeri race had a 1% frequency of homozygote genotype, whereas the homozygote genotype was not found in other ethnicities. On the other hand, the Kurds (11%) and the Persian Gulf Islanders (1%) had the highest and lowest frequency of heterozygote genotype among the Iranian population, respectively. In the Iranian population, the mean frequency of CYP2C8 homozygous and heterozygous genotypes based on the *4 allele was 0.1% and 5.1%, respectively. The prevalence of the *2 allele ranged from 6% in the Persian Gulf Islanders to 0% in Turkmen. The frequency of the *2 allele among the Lur was similar to the Caucasian race and the European population ^[43][54]. Additionally, a genotypic study of Iranian ethnics revealed that only Persian Gulf Islanders and Baloch had a 1% frequency of the homozygote genotype. Other ethnicities, on the other hand, did not have the homozygote genotype. In the Iranian population, the mean frequency of CYP2C8 homozygous and heterozygous genotypes based on *2 allele was 0.2% and 4.2%, respectively.

5. CYP2C9

According to the previous study ^[32][37], the *1 allele had a 78.1% prevalence. Among Iranian ethnicities, the *2 allele prevalence ranged from 15% in Lur to 7% in Arab. None of the Iranian ethnicities had the same frequency of the *2 allele as the Caucasian race. However, the frequency of this allele among Azeris was similar to the European population ^[35][55]. Moreover, regarding *2 allele frequency, the Azeri and Turkmen were similar to the Middle Eastern population ^{[37][44][45][46]}[40,41,43,46]. Additionally, a genotypic study of Iranian ethnics revealed that Persian and Persian Gulf Islanders had the highest homozygote genotype (2%), while Lur, Turkmen, Kur, and Baloch did not. Among Iranian ethnicities, the *3 allele prevalence ranged from 14.5% in Baloch to 7% in Arabs. None of the Iranian ethnicities had a frequency of the *2 allele similar to the Caucasian race. However, the frequency of this allele among the Azeri and Arab populations was similar to the European population ^[35][55]. Moreover, except for Baloch and Persian Gulf Islanders, all Iranian ethnicities were similar to the Middle Eastern population in terms of the *3 allele frequency ^{[37][44][45][46]}[40,41,43,46]. Additionally, a genotypic study of Iranian ethnicities revealed that Baloch had the highest frequency of homozygote genotype (5%), while Arab and Azeri did not. On the other hand, the Persian Gulf Islanders (21%) and Arab and Kurds (14%) had the highest and lowest frequency of heterozygote genotype among the Iranian population, respectively.

6. CYP2C19

The frequency of the *1 allele in the Iranian population was 85.8% ^[32][37]. The only allele with a frequency of more than 1% among the Iranian population was the *2 allele. Its prevalence ranged from 18% in the Baloch to 11% in the Azeri, Lur, Kurd, and Persian Gulf Islanders. The frequency of the *2 allele was similar in the Arabs and Caucasians. However, among the Persian and Turkmen, its frequency was similar to the European population ^[35][55]. Moreover, the Baloch was similar to the Middle Eastern population regarding the *2 allele frequency ^{[37][38][46][47]}[40,45,46,49]. Additionally, genotypic analysis of these ethnicities revealed that the Baloch (4%) and Fars, Arab, and Lur (2%) had the highest and lowest frequency of homozygote genotypes, respectively. In comparison, the Persian (29%) and Persian Gulf Islander (16%) populations had the highest and lowest frequency of heterozygote genotype, respectivel. In the Iranian population, the mean frequency of CYP2C19 homozygous and heterozygous genotypes based on the *2 allele was 2% and 22.3%, respectively.

7. CYP2D6

A previous study found that the frequency of the *1 allele in the Iranian population was 10.6% ^[32][37]. The prevalence of the *2 allele was the highest in the Iranian population (47%), ranging from 53% in Baloch to 42% in Azeri. The frequency of the *2 allele among all Iranian ethnics was similar to the Caucasian race ^[35][55]. However, none were similar to the Middle Eastern population ^[48][49][50][39,48,51]. Furthermore, a genotypic analysis of these ethnicities revealed that the Baloch (32%) and Azeri (17%) had the highest and lowest frequency of homozygote genotype, respectively. In comparison, the Azeri (50%) and Lur (38.3%) had the highest and lowest frequency of heterozygote genotype, respectively. In the Iranian population, the mean frequency of CYP2D6 homozygous and heterozygous genotypes based on the *2 allele was 24.4% and 45.3%, respectively. The *10 allele prevalence ranged from 22.5% in Azeris to 10% in the Arabs. None of the Iranian ethnics had the same frequency of the *10 allele as the Caucasian race, the European population ^[35][55] or the Middle Eastern population ^[48][49][50][39,48,51]. Additionally, genotypic analysis of these ethnicities revealed that the Azeri (7%) and Lur, Arab, and Persian Gulf Islander (1%) had the highest and lowest frequency of homozygote genotype, respectively. In comparison, the Azeri (31%) and Baloch (17%) had the highest and lowest frequency of heterozygote genotype, respectively. In the Iranian population, the mean frequency of CYP2D6 homozygous and heterozygous genotypes based on the *10 allele was 3.1% and 24%, respectively. The *41 allele prevalence ranged from 18.5% in the Persian to 8.5% in the Persian Gulf Islander. The frequency of the *41 alleles among Turkmen and Persian Gulf Islander was similar to the Caucasian race and Turkmen to the European population ^[51][53]. Furthermore, except for Turkmen and Persian Gulf Islanders, the frequency of this allele was comparable to the Middle Eastern population ^[48][49][50][39,48,51]. Additionally, a genotypic analysis of these ethnicities revealed that Azeri, Kurd, Lur, and Baloch (4%) and Arab (1%) had the highest and lowest homozygote genotypes, respectively. In comparison, Azeri (29%) and Baloch (11%) had the highest and lowest frequency of heterozygote genotype, respectively. In the Iranian population, the mean frequency of CYP2D6 homozygous and heterozygous genotypes based on the *41 allele was 3.1% and 21.7%, respectively. With a prevalence of more than 1%, the *4 alleles had the lowest frequency among CYP2D6 alleles. None of the Iranian ethnicities had the same frequency of the *4 allele as the Caucasian race or the European population ^[35][55]. However, the frequency of this allele among Kurds and Turkmen was similar to the Middle Eastern population ^[48][49][50][39,48,51]. Additionally, the Azeri (17%) and the Arab (7.5%) had this allele’s highest and lowest frequency. According to the genotypic analysis of these races, Azeri (4%) and Lur lacked the homozygote genotype. In comparison, Azeri (26%) and Turkmen (12.1%) had the highest and lowest frequency of heterozygote genotype, respectively. In the Iranian population, the mean frequency of CYP2D6 homozygous and heterozygous genotypes based on the *4 allele was 1.7% and 19%, respectively.

8. CYP2E1

The *1 allele frequency in the Iranian population was 94.1% ^[32][37]. The *4 allele, with a 5.6% frequency in the Iranian population, is the only one with a frequency of more than 1%. None of the Iranian ethnicities had the same frequency of the *4 allele as the European population. At the same time, the Azeri was similar to the Middle Eastern population regarding the *4 allele frequency [46]. The Persian (8%) and the Azeri (3.5%) also had this allele’s highest and lowest frequency, respectively. The homozygote genotype was found only in Kurds and Lurs (1%), with no other ethnicities having this allele. In addition, the Persian (16%) and the Azeri (7%) had the highest and lowest frequency of heterozygote genotype, respectively. In the Iranian population, the mean frequency of CYP2E1 homozygous and heterozygous genotypes based on the *4 allele was 0.3% and 10.7%, respectively.

9. CYP3A4

In the Iranian population, the prevalence of the *1 allele was 99.7% ^[32][37]. The frequency of mutated alleles of the CYP3A4 enzyme was less than 0.5% among the Iranian population.

10. CYP3A5

According to the previous research, the prevalence of the *1 allele in the Iranian population was 3.8% ^[32][37]. The *3 allele, with a 96.1% frequency in the Iranian population, was the only one with a frequency of more than 1%. The frequency of the *3 allele among all Iranian ethnicities, except Persian, Turkmen, and Lur, was similar to the Caucasian race ^[35][55] while showing no similarity with the European or Middle Eastern populations ^[52][53][38,42]. The Persian (98.2%) and the Arab (94.8%) had this allele’s highest and lowest frequencies, respectively. Genotypic analysis of these ethnicities revealed that the Persian (99%) and Arab (88%) had the highest and lowest frequency of homozygote genotypes, respectively. In comparison, the Arab (11%) and Persian (0%) had the highest and lowest frequency of heterozygote genotype, respectively. In the Iranian population, the mean frequency of CYP3A5 homozygous and heterozygous genotypes based on the *3 allele was 93.9% and 5.8%, respectively.