CYP2S1 gene polymorphisms in a Korean population.
Cytochrome P450 2S1 (CYP2S1) is a drug-metabolizing enzyme that shows interindividual variations in response to treatments for psoriasis and is regarded as a putative prognostic marker for colorectal cancer treatment. To gain insight into the genetic basis for the interindividual variations, CYP2S1 gene polymorphisms were analyzed in Korean subjects. Using direct sequencing of the CYP2S1 gene, 12 genetic variations, which included the two novel nonsynonymous mutations CYP2S1 S61N (0.3%) and CYP2S1 L230R (0.8%), were identified in 50 Korean subjects. Homology modeling predicted the location of the L230R change to be near two conserved alpha-helices in the hood of the substrate-binding site. Linkage disequilibrium (LD) analysis with seven common CYP2S1 variations showed two discrete LD blocks in CYP2S1 gene and consequently a limited number of haplotypes. Although the importance of novel CYP2S1 variants and haplotypes remains to be discovered, CYP2S1 polymorphisms would provide useful information on interindividual variations with respect to CYP2S1 function, which facilitates drug response predictions and disease prognosis.
Jang
Yin-Jin
YJ
Department of Pharmacology, Inje University College of Medicine, Gaegum-dong, Jin-gu, Busan, Korea.
Cha
Eun-Young
EY
Kim
Woo-Young
WY
Park
Seong Wook
SW
Shon
Ji-Hong
JH
Lee
Sang Seop
SS
Shin
Jae-Gook
JG
D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005828:Genetics, Population; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007723:Korea / Q000208:ethnology; D015810:Linkage Disequilibrium / Q000235:genetics*; D008958:Models, Molecular; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*
D003577:Cytochrome P-450 Enzyme System; C422564:CYP2S1 protein, human