*9.3. Genetic Variants of Other CYP4 Genes*

Genetic polymorphism studies of *CYP4V2* with respect to BCD are described above. In addition to BCD, genome-wide analysis found that a *CYP4V2* genetic variant was strongly associated with deep vein thrombosis [162], which was confirmed later in multiple studies [163,164]. Association of the genetic variant 7234C>A (rs13146272) on exon 6 of the *CYP4V2* gene with the risk of deep venous thrombosis and tamoxifen-induced venous thrombosis has been reported [165]. The exact mechanism through which the *CYP4V2* gene defect increases the risk of deep vein thrombosis remains poorly understood. This genetic variant substitutes polar glutamine with basic lysine at position 259 of the CYP4V2 amino acid sequence, which may influence its activity. Genetic studies of *4Z1* and *4X1* are scarce, as these genes were recently identified and their physiological roles remain unclear. CYP4X1 was found to convert the endocannabinoid anandamide, an important signaling molecule in the neurovascular cascade, into a single monooxygenated product (14,15-epoxyeicosatrienoic ethanolamide), suggesting a potential role in brain signaling [40]. High levels of mRNA expression of CYP4X1 were found in the skin, brain, heart, liver, prostate, and breast [40] and CYP4Z1 mRNA was preferentially expressed in mammary tissue [21]. Functional analysis of CYP4Z1 indicated that CYP4Z1 has catalytic activity toward lauric and arachidonic acids, but 20-HETE was not detected in arachidonic acid metabolism [87]. Major genetic polymorphisms in *CYP4* genes with clinical impact were summarized in Table 2.



*Int. J. Mol. Sci.* **2019**, *20*, 4274
