CYP2C19 genotypes in a population of healthy volunteers and in children with hematological malignancies in Gaza Strip.
BACKGROUND
Cytochrome P450 2C19 (CYP2C19) participates in the metabolism of many clinically important drugs and xenobiotic compounds. Genetic polymorphisms of the CYP2C19 gene are described to have possible effect on drug treatment and increasing susceptibility to carcinogenic substances. The aim of this study was to determine the frequencies of the common polymorphic CYP2C19 alleles (CYP2C19*2 and CYP2C19*3) in Gaza Strip population and to investigate their association with occurrence of childhood hematological malignancies as compared to healthy subjects.


METHODS
The polymorphism of CYP2C19 was analyzed by PCR-RFLP. DNA was extracted from blood samples obtained from 52 previously diagnosed hematological malignancy children and 200 normal subjects.


RESULTS
In the patient group the frequencies of CYP2C19*2 and CYP2C19*3 were 9.62% and 0.96%, respectively; while in the control group the respective frequencies were 5.75% and 3%. There is no significant difference between the healthy and the patient groups in terms of the frequencies of CYP2C19*2 and CYP2C19*3. The genotyping analysis showed the following results: 15.39% (1*/2*), 1.92% (1*/3*), 1.92% (2*/2*) and 80.77% (1*/1*) in the patients, while in the normal subjects the distribution of CYP2C19*1/*1, *1/*2, *1/*3, *2/*2, *2/*3 and *3/*3 genotypes were 86.5, 6.5, 3, 1.5, 2, and 0.5 %, respectively.


CONCLUSIONS
There is no significant association between the CYP2C19 polymorphism and the occurrence of the childhood hematological malignancies. The distribution of CYP2C19*2 in the Gaza Strip population is lower than that in Caucasians, Africans and the Asian populations. The CYP2C19*3 allele, which was not reported in the Caucasian populations, is present in 3% of the Gaza Strip population. Further studies are needed to investigate the role of other CYPs' polymorphisms in our patient group.
Sameer
Abu-Eid I
AE
European Gaza Hospital, Laboratory Department, IUG- Gaza, Palestinian Authority. sameer_eid@yahoo.com
Amany
Gharbieh M
GM
Abdela
Abed A
AA
Fadel
Sharif A
SA
D000328:Adult; D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D002648:Child; D065731:Cytochrome P-450 CYP2C19; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005828:Genetics, Population / Q000379:methods*; D005838:Genotype; D019337:Hematologic Neoplasms / Q000208:ethnology* / Q000235:genetics*; D006801:Humans; D008297:Male; D008877:Middle East / Q000208:ethnology; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length
D004273:DNA, Neoplasm; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19