Genetic polymorphism of CYP2U1, a cytochrome P450 involved in fatty acids hydroxylation.
The human cytochrome P450 2U1 (CYP2U1) has been described as a novel extrahepatic P450. CYP2U1 is a highly conserved gene mainly expressed in brain and thymus, but also at lower levels in kidney, lung or heart. This selective tissue distribution suggests important endogenous functions, in particular in the conversion of arachidonic acid into two bioactive compounds, the 19- and 20-HETE. To investigate the extent of CYP2U1 genetic polymorphism in 70 French individuals, a screening for sequence variations in the 5'-flanking and protein encoding regions was performed using PCR-SSCP and sequencing strategies. Four polymorphisms were identified and correspond to -204C>A and -241T>C in the 5'-flanking region, -37G>A in the 5'-untranslated region, and IVS2-17T>C in the intron 2. The most frequent mutations, -241T>C (59.7%) and IVS2-17T>C (66.0%), did not seem to alter CYP2U1 lung expression. These results suggest that CYP2U1 exhibits few genetic variations and support a probable role in endogenous processes.
Devos
Aurore
A
EA2679, Faculté de Médecine, Pôle Recherche, Université Lille Nord de France, France.
Lino Cardenas
Christian Lacks
CL
Glowacki
François
F
Engels
Anne
A
Lo-Guidice
Jean-Marc
JM
Chevalier
Dany
D
Allorge
Delphine
D
Broly
Franck
F
Cauffiez
Christelle
C
D001921:Brain / Q000201:enzymology; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000235:genetics*; D000072467:Cytochrome P450 Family 2; D005260:Female; D005602:France; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics*; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000235:genetics / Q000378:metabolism*; D006900:Hydroxylation; D008168:Lung / Q000201:enzymology; D008297:Male; D009154:Mutation; D011110:Polymorphism, Genetic; D013950:Thymus Gland / Q000201:enzymology
D006893:Hydroxyeicosatetraenoic Acids; C055986:19-hydroxy-5,8,11,14-eicosatetraenoic acid; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D003577:Cytochrome P-450 Enzyme System; C484320:CYP2U1 protein, human; D000072467:Cytochrome P450 Family 2