Cytochrome P450 CYP2C19 genotypes in Nigerian sickle-cell disease patients and normal controls.
OBJECTIVE
Subjects with different CYP2C19 genotypes may metabolize proguanil, a pro-drug used for malaria prophylaxis differently and the frequency of the different alleles may be different in patients with sickle-cell disease (SCD) and normal controls. The objective of this study was to evaluate CYP2C19 *1, *2 and *3 allele and genotype frequencies in Nigerian normal controls and SCD patients, and to further compare variant CYP2C19 frequencies in Nigerians with other African populations.


METHODS
Genotyping was carried out with PCR and restriction fragment length polymorphism analysis.


CONCLUSIONS
CYP2C19 *1 (84·3 vs. 84·9%) or *2 allele frequency (15·7 vs. 15·1%) was not significantly different between patients with SCD and normal subjects. No *3 allele was detected in the cohort. The SCD group exhibited a statistically significantly lower frequency of *1/*1 genotype (69·6%) compared with normal controls (74·4%). Frequency of *2/*2 was significantly lower in SCD (0·9%) compared with normal controls (4·7%). Frequencies of *1/*2 (29·6 vs. 20·9%) were no different in SCD and normal controls.


CONCLUSIONS
Prevalence of CYP2C19 polymorphisms was defined for the first time in Nigerian normal and SCD populations. Nigerian SCD patients exhibited significantly lower CYP2C19 *1/*1 and *2/*2 frequencies than normal controls. No differences were detected in CYP2C19 allele or genotype frequencies in normal subjects between this study and previous reports in other African populations.
Babalola
C P
CP
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Ibadan, Ibadan, Oyo State, Nigeria.
Adejumo
O
O
Ung
D
D
Xu
Z
Z
Odetunde
A
A
Kotila
T
T
Falusi
A G
AG
Nagar
S
S
D000293:Adolescent; D000328:Adult; D000483:Alleles; D000755:Anemia, Sickle Cell / Q000201:enzymology* / Q000235:genetics; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D044383:Black People; D002648:Child; D065731:Cytochrome P-450 CYP2C19; D005260:Female; D005787:Gene Frequency; D005828:Genetics, Population; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009549:Nigeria; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic
D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19