title: Characterization of an allelic variant in the nifedipine-specific element of CYP3A4: ethnic distribution and implications for prostate cancer risk. Mutations in brief no. 191. Online.
abstract: CYP3A4 is involved in the metabolism of numerous biologically active compounds, including testosterone. A genetic variant located in the P450NF (nifedipine) specific element (NFSE) has been identified that disrupts a transciptional regulatory element located in the 5' regulatory region of CYP3A4. The CYP3A4 variant (CYP3A4-V) is associated with the clinical presentation of prostate cancer. There are significant differences in CYP3A4 metabolism and rates of prostate cancer across ethnic groups that may be associated with CYP3A4 genotypes. Therefore, we estimated the frequency of the CYP3A4 variant in three ethnic groups with different prostate cancer incidence rates. The frequency (q) of CYP3A4-V was significantly different (p<0.0001) in African Americans (q=0.53), U.S. Caucasians (q=0.09), and Taiwanese (q=0.0). CYP3A4-V segregated in a Mendelian manner in one large African American family, and 7 of 16 (44%) biologically unrelated "marry-ins" carried a CYP3A4 variant allele. Reflecting population-specific prostate cancer incidence rates, our results suggest a high frequency of this variant in African Americans compared with U.S. Caucasians and Taiwanese.
authors.affiliation: Department of Biostatistics and Epidemiology, Center for Clinical Epidemiology and Biostatistics, Philadelphia 19104, Pennsylvania, USA.
authors.forename: A H
authors.initials: AH
authors.lastname: Walker
authors.forename: J M
authors.initials: JM
authors.lastname: Jaffe
authors.forename: S
authors.initials: S
authors.lastname: Gunasegaram
authors.forename: S A
authors.initials: SA
authors.lastname: Cummings
authors.forename: C S
authors.initials: CS
authors.lastname: Huang
authors.forename: H D
authors.initials: HD
authors.lastname: Chern
authors.forename: O I
authors.initials: OI
authors.lastname: Olopade
authors.forename: B L
authors.initials: BL
authors.lastname: Weber
authors.forename: T R
authors.initials: TR
authors.lastname: Rebbeck
mesh_terms: D000483:Alleles; D044466:Asian People / Q000235:genetics; D044383:Black People / Q000235:genetics; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D008297:Male; D006899:Mixed Function Oxygenases / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000208:ethnology* / Q000235:genetics*; D012307:Risk Factors; D044465:White People / Q000235:genetics; D001741:Black or African American
chemical_list: D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human