Sequence diversity and haplotype structure at the human CYP3A cluster.

The four members of the human CYP3A subfamily play important roles in the clearance of xenobiotics, hormones, and environmental compounds. Many SNPs at the CYP3A locus have been characterized, with several showing large allele frequency differences across populations. In addition to the effects of CYP3A SNPs on drug metabolism, recent studies have highlighted the potential for CYP3A variation in susceptibility to several common phenotypes, including hypertension and cancer. We previously showed that the CYP3A4 and CYP3A5 genes have a strong haplotype structure at varying frequencies across ethnic groups. Here, we extend our re-sequencing survey to the remaining CYP3A genes in the same cluster, CYP3A7 and CYP3A43. Our study identified a large number of SNPs in coding and conserved noncoding sequences, several of which are common. The combined data set allows us to investigate patterns of sequence variation and linkage disequilibrium at the entire CYP3A locus for use in future association studies.