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Blood, 15 October 2001, Vol. 98, No. 8, pp. 2584-2587
BRIEF REPORT
Genetic polymorphism in exon 4 of cytochrome P450 CYP2C9 may be
associated with warfarin sensitivity in Chinese patients
Anskar Y. H. Leung,
Howard C. H. Chow,
Y. L. Kwong,
Albert K. W. Lie,
Alvin T. K. Fung,
W. H. Chow,
Alex S. B. Yip, and
Raymond Liang
From the Division of Haematology and Oncology,
Department of Medicine, The University of Hong Kong.
CYP2C9 polymorphisms reported in Caucasians
(Arg144Cys in exon 3 and Ile359Leu in exon 7) are extremely
uncommon in Chinese persons. The genotype of CYP2C9 in this
population was characterized to investigate its relation with the
interindividual variation in warfarin dosages. Eighty-nine Chinese
patients receiving warfarin were recruited. Target sequences in
CYP2C9 in exons 1, 4, and 5 were amplified by polymerase
chain reaction, followed by direct sequencing. Polymorphisms at 4 positions were demonstrated in exon 4. Heterozygosities for 608TTG>GTG
(Leu208Val), 561CAG>CCG (Gln192Pro), 537CAT>CCT (His184Pro), and
527ATT>CTT (Ile181Leu) existed at frequencies 0.75, 0.20, 0.10, and
0.09, respectively. Seventeen patients (frequency, 0.19) were
homozygous for Val208. The common genotypic combinations at these loci
are Ile181/His184/Gln192/Leu208Val (n = 50),
Ile181/His184/Gln192/Val208 (n = 15),
Ile181/His184/Gln192/Leu208 (n = 4),
Ile181/His184/Gln192Pro/Leu208Val (n = 6),
Ile181/His184Pro/Gln192Pro/Leu208Val (n = 4), and
Ile181Leu/His184/Gln192Pro/ Leu208Val (n = 4). At codon 208, heterozygous Leu208Val and homozygous Val208 appeared to have a lower
warfarin dose requirement than the homozygous Leu208. Patients who are heterozygous for Ile181Leu had a
higher warfarin dose requirement than the homozygous Ile181. Amplified sequences in exons 1 and 5 did not exhibit polymorphism. In conclusion, Chinese patients showed genetic polymorphisms of CYP2C9 in
exon 4 and at codon 208; most were heterozygous Leu208Val and
homozygous Val208. Homozygous Leu208, a common allele in Caucasians, is
uncommon in this cohort. The significance of these CYP2C9
polymorphic alleles remains to be determined.
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