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. 2022 Mar 5;44(3):599–607. doi: 10.1007/s11096-022-01386-8

Table 1.

Most prominent genetic variants affecting warfarin dose

Gene CYP2C9 VKORC1 CYP4F2 CYP2C GGCX CALU
Location [41] Chromosome 10 Chromosome 16 Chromosome 19 Chromosome 10 Chromosome 2 Chromosome 7
Function [6] Encodes for CYP2C9 enzyme which metabolises the more active S-warfarin. Encodes for VKOR enzyme which changes oxidized vitamin k into reduced (active) vitamin k, which activates the clotting factors. Encodes for CYP4F2 enzyme which deactivates the reduced form of vitamin k. Intergenic cluster, could affect CYP2C9 gene activity. Encodes for GGCX enzyme which activates the coagulation factors. Encodes for CALU protein which chaperon GGCX enzyme.
Common variants and most prevalent race [6, 34]

CYP2C9*2 (rs1799853): Missense variant.: in Caucasians.

CYP2C9*3 (rs1057910) Missense variant: in Caucasians.

CYP2C9*5 (rs28371686) Missense variant: in Africans.

CYP2C9*6 (rs9332131) Frameshift variant: in Africans.

CYP2C9*8 (rs7900194) Missense variant: in Africans.

CYP2C9*11 (rs28371685) Missense variant: in Africans.

VKORC1 c.-1639G > A upstream single nucleotide variant.:

AA: common in Asian population

AG: common in Caucasian population.

GG: common in African population.

CYP4F2*3 (rs2108622)Missense variant: Most common in Asians and Caucasians and associated with a higher warfarin maintenance dose.

SNP (rs12777823)

Most prevalent in Africans and associated with a lower warfarin maintenance dose.

Non-synonymous variant (rs11676382).

Prevalent in Caucasian and associated with lower warfarin maintenance dose. [42]

Intronic SNP

(rs339097)

Associated with higher warfarin maintenance dose in Africans. [43]

CALU: Calumenin, CYP2C9: Cytochrome 450 2C9, CYP4F2*3: Cytochrome 450 4F2*3, GGCX: Gamma glutamyl carboxylase, SNP: Single nucleotide polymorphism, ,VKORC1: Vitamin k epoxide reductase complex 1