Variant:

rs890293 at chr1:60392494 in CYP2J2 (VIP)

VIP Variant in CYP2J2

CYP2J2 variants have been characterized [Article:15861034], [Article:11901223], [Article:16868033]. The Human Cytochrome P450 Nomenclature Committee recognizes ten CYP2J2 alleles on its website http:www.cypalleles.ki.se.

By far, the best-studied of these is CYP2J2*7, which was first identified by King et al. [Article:11901223] in a sequencing project to identify CYP2J2 variants. CYP2J2*7 is the most common known functional CYP2J2 variant, occurring at frequencies of 2.1%-17% (see Table 1). The defining SNP for CYP2J2*7, (rs890293), is located in the proximal promoter of CYP2J2, substituting a "T" for the "G" found in the wild-type gene [Article:11901223]. This SNP, located 76 nucleotides upstream of the first nucleotide of the translation start codon and 50 nucleotides upstream of the transcription start site, disrupts a binding site for the SP1 transcription factor [Article:15466638], [Article:11901223]. In vitro assays showed that transcription was reduced 50% in CYP2J2*7 promoter-reporter gene constructs relative to that observed for the wild-type CYP2J2 promoter [Article:15466638].

Since CYP2J2*7 is the most common functional CYP2J2 polymorphism discovered, many studies have looked for associations between CYP2J2*7 and various diseases and phenotypes. However, due to conflicting results from different studies, there is not yet a clear consensus on the in vivo effects of CYP2J2*7. Several clinical studies investigated the association of CYP2J2*7 with different cardiovascular and cerebrovascular diseases. The findings are summarized in Table 2.

In addition, a case-control study of a predominately Caucasian population found two CYP2J2 intronic tag SNPs, (rs10889160) and (rs11572325), associated with increased risk of myocardial infarction [Article:18496133]. Both SNPs were in moderate linkage disequilibrium (LD) with the CYP2J2*7 allele. Interestingly, (rs4388726), the tag SNP in the strongest LD with the CYP2J2*7 polymorphism, showed no significant association with myocardial infarction [Article:18496133]. This study found no association between these genetic variations in CYP2J2 and ischemic stroke [Article:18496133].

Other CYP2J2 alleles:
Recombinant CYP2J2 proteins individually engineered to contain the polymorphisms seen in CYP2J2*2, CYP2J2*3, and CYP2J2*6 each exhibited reduced metabolism of AA and LA [Article:11901223]. Recombinant protein carrying the CYP2J2*4 polymorphism demonstrated reduced metabolism of AA only [Article:11901223]. CYP2J2*5 recombinant protein produced wild-type levels of AA and LA metabolites [Article:11901223]. Recombinant CYP2J2*8 showed almost complete loss of enzymatic activity as determined by CYP2J2-catalyzed astemizole O-demethylation and ebastine hydroxylation, while recombinant CYP2J2*9 showed enzymatic activities comparable with wild-type CYP2J2 [Article:15861034]. CYP2J2*10, documented in only one individual, is hypothesized to encode a reduced-function protein [Article:16868033].

Note: The CYP2J2 gene is found on the minus chromosomal strand. Please note that for standardization, the PharmGKB presents all allele base pairs on the positive chromosomal strand, therefore the alleles within our variant annotations will differ (in a complementary manner) from those in this VIP summary that are given on the minus strand as reported in the literature.

Table 1: Allele Frequency Table

Table 2: CYP2J2*7 association with different disease risks

Publications related to rs890293 at chr1:60392494: 2

VIP	Cloning of CYP2J2 gene and identification of functional polymorphisms. Molecular pharmacology. 2002. King Lorraine M, et al. [Article:11901223@PubMed]
VIP	Molecular cloning and expression of CYP2J2, a human cytochrome P450 arachidonic acid epoxygenase highly expressed in heart. The Journal of biological chemistry. 1996. Wu S, et al. [Article:8631948@PubMed]

Cross-References

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