Lack of mutations in CYP2D6 and CYP27 in patients with apparent deficiency of vitamin D 25-hydroxylase.
Activation of vitamin D requires hepatic 25-hydroxylation and renal 1alpha-hydroxylation. Defects in renal P450c1alpha are well-described, but few patients with defective vitamin D 25-hydroxylation are reported. The cytochrome P450 enzymes CYP2D6 and CYP27 are potential 25-hydroxylases. We sequenced both genes in two reported families with hepatic 25-hydroxylase deficiency and found no mutations. 25-Hydroxylation occurs in both mitochondria and microsomes. The existence genes encoding distinct enzymes would provide genetic redundancy, explaining the rarity of apparent vitamin D 25-hydroxylase deficiency.
Lin
Chin Jia
CJ
Department of Pediatrics, University of California, San Francisco, CA 94143-0978, USA.
Dardis
Andrea
A
Wijesuriya
Sujeewa D
SD
Abdullah
Mohamed A
MA
Casella
Samuel J
SJ
Miller
Walter L
WL
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000172:deficiency*; D053493:Cholestanetriol 26-Monooxygenase; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D006801:Humans; D008664:Metal Metabolism, Inborn Errors / Q000235:genetics*; D008861:Microsomes / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D009154:Mutation; D013250:Steroid Hydroxylases / Q000235:genetics*
D013250:Steroid Hydroxylases; D019389:Cytochrome P-450 CYP2D6; C506831:CYP27A1 protein, human; D053493:Cholestanetriol 26-Monooxygenase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase