CYP1A2 is more variable than previously thought: a genomic biography of the gene behind the human drug-metabolizing enzyme.

Background And Objectives: CYP1A2 metabolizes various drugs, endogenous compounds and procarcinogens. As human genetic diversity has been reported to decrease with distance from Ethiopia, we resequenced CYP1A2 in five Ethiopian ethnic groups representing a rough northeast to southwest transect across Ethiopia to establish: (i) what variation exists in comparison with what is already known globally and (ii) what CYP1A2 pharmacogenetic profiles may be present as several CYP1A2-metabolized drugs are administered to Ethiopians.

Results And Conclusions: We found 49 different variable sites (30 of which are novel), nine nonsynonymous changes (seven of which are novel), one synonymous change and 55 different haplotypes, only three of which are previously reported.

Multiple rare variants as a cause of a common phenotype: several different lactase persistence associated alleles in a single ethnic group.

Persistence of intestinal lactase into adulthood allows humans to use milk from other mammals as a source of food and water. This genetic trait has arisen by convergent evolution and the derived alleles of at least three different single nucleotide polymorphisms (-13910C>T, -13915T>G, -14010G>C) are associated with lactase persistence in different populations. Each allele occurs on an extended haplotype, consistent with positive directional selection.