Analysis of humanCYP1A1andCYP1A2genes and their shared bidirectional promoter in eight world populations

Abstract

The human CYP1A1_CYP1A2 locus comprises the CYP1A1 (5,988 bp) and CYP1A2 (7,759 bp) transcribed regions, oriented head-to-head, sharing a bidirectional promoter of 23,306 bp. The older CYP1A1 gene appears more conserved and responsible for critical life function(s), whereas the younger CYP1A2 gene might have evolved more rapidly due to environmental (dietary) pressures. A population genetics study might confirm this premise. We combined 60

PharmGKB summary

“…CYP1A2 is constitutively highly expressed in liver and is inducible in the liver, lung, pancreas, gastrointestinal tract, and brain [7]. Drug–drug interactions and interactions with smoking have been reported to alter drug response [1].…”

Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption

“…The C allele of rs4410790 is also positively correlated with cerebellum AHR methylation, suggesting a novel role of Ahr in motor or learning pathways that may trigger coffee consumption. The most significant variants at 15q24 reside in the CYP1A1-CYP1A2 bidirectional promoter where AHR response elements have been identified and shown to be important for transcriptional activation of both CYP1A1 and CYP1A2 23 . The rs2472297 T variant putatively weakens the binding of SP1, a co-activator in the Ahr-Arnt complex regulating CYP1 locus transcription 24 and is also implicated in the expression of several neighboring genes.…”

Regulation of Human Cytochrome P4501A1 (hCYP1A1): A Plausible Target for Chemoprevention?

“…The 5′ flanking region is shared by both genes and contains a bidirectional promoter and DNA motifs, known as response elements, that activate and regulate the expression of these genes [20, 21]. …”

“…Some in silico studies have been conducted in order to determine a possible regulation of CYP1A through noncoding RNAs. Based on web databases analyses, six putative micro RNAs (miRNAs), hsa-miR-125b-2, hsa-miR-488, hsa-miR-657, hsa-miR-892a, hsa-miR-511, and hsa-miR-626, with one or more binding sites to the 3′UTR region of hCYP1A1 were identified [21]. Following the same strategy, an additional study used five different bioinformatics programs and predicted 332 miRNAs to target hCYP1A1 UTRs, from which 12% were predicted in at least 2 programs [110].…”