Disease relevance of CYP3A43

• The N terminus of CYP3A43 was modified for efficient expression of the protein in Escherichia coli, and a 6X histidine tag was added at the C terminus to facilitate purification [1].
• The observation that CYP3A4 and CYP3A43 were associated with prostate cancer, are not in linkage equilibrium, and are both involved in testosterone metabolism, suggest that both CYP3A4*1B and CYP3A43*3 may influence the probability of having prostate cancer and disease severity [2].

High impact information on CYP3A43

• The enzyme products of CYP3A4 and CYP3A43 are involved in testosterone metabolism [2].
• CYP3A4, CYP3A5, and CYP3A43 genotypes and haplotypes in the etiology and severity of prostate cancer [2].
• Using quantitative real-time polymerase chain reaction, the ratio of one CYP3A43/3A4 intergenic combination was estimated to be approximately 0.15% that of the CYP3A43 mRNAs [3].
• CYP3A43 gave a reduced carbon monoxide difference spectra with an absorbance maximum at 450 nm [1].
• Immunoblot analyses revealed that CYP3A43 comigrates with CYP3A4 in polyacrylamide gel electrophoresis but does separate from CYP3A5 [1].

Biological context of CYP3A43

• Heterologous expression of the chimeric species composed of CYP3A43 exon 1 joined to exons 2-13 of CYP3A4 revealed catalytic activity toward testosterone [3].
• Cloning and tissue distribution of a novel human cytochrome p450 of the CYP3A subfamily, CYP3A43 [4].
• Analysis of restriction fragment length polymorphism is proposed for detecting CYP3A43 gene c1047 > T mutation [5].
• A screening for sequence variations in the 5'-flanking and protein coding regions of the CYP3A43 gene was performed by a Polymerase Chain Reaction - Single Strand Conformational Polymorphism (PCR-SSCP) strategy, using DNA samples from 48 unrelated French individuals [6].
• First report of a genetic polymorphism of the cytochrome P450 3A43 (CYP3A43) gene: identification of a loss-of-function variant [6].

Anatomical context of CYP3A43

• CYP3A43 expression was detected in liver, kidney, pancreas, and prostate [1].
• It is concluded that CYP3A43 mRNA is expressed mainly in liver and testis and that the protein would not contribute significantly to human drug metabolism [4].
• The CYP3A43 cDNA was heterologously expressed in yeast, COS-1 cells, mouse hepatic H2.35 cells and in human embryonic kidney (HEK) 293 cells, but in contrast to CYP3A4 which was formed in all cell types, no detectable CYP3A43 protein was produced [4].
• In the endometrium, CYP3A4 and CYP3A43 are down-regulated by estrogen, whereas CYP3A5 is expressed at higher levels during the secretory phase [7].

Associations of CYP3A43 with chemical compounds

• The highest expression level of CYP3A43 mRNA is observed in the prostate, an organ with extensive steroid metabolism [8].
• A cytosine-to-guanine polymorphism in CYP3A43 results in a proline-to-alanine substitution at codon 340 [9].

Other interactions of CYP3A43

• CYP3A5 and CYP3A7 each contributed on average 2%, whereas CYP3A43 contributed 0.3% transcripts to this pool [10].

Analytical, diagnostic and therapeutic context of CYP3A43

• Gene specific PCR of cDNA from extrahepatic tissues showed, with the exception of the testis, only low levels of CYP3A43 expression [4].
• In a case-control study with 490 incident prostate cancer cases (124 African Americans and 358 Caucasians) and 494 controls (167 African Americans and 319 Caucasians), we examined the association between CYP3A43 Pro(340)Ala polymorphism and prostate cancer risk [9].

References