Identification of CYP19A1 single-nucleotide polymorphisms and their haplotype distributions in a Korean population

Aromatase, encoded by the CYP19A1 gene, is a key enzyme in the biosynthesis of estrogen. In an effort to screen for CYP19A1 single-nucleotide polymorphisms (SNPs) in Koreans, the CYP19A1 gene was directly sequenced in 50 normal subjects. A total of 19 variations were identified: four in exons, ten in introns, six in the 5'-untranslated region (UTR) and one in 3'-UTR. The distribution of CYP19A1 (TTTA)(n) polymorphisms was such that the most frequent allele was (TTTA)(7) (66%), followed by (TTTA)(11) (30%), (TTTA)(12) (3%) and (TTTA)(13) (1%). The order of the frequency distribution of CYP19A1 variations, other than that of the (TTTA)(n) variant, was IVS6-106T>G and IVS7-79A>G (57%); 1531C>T (56%); IVS5-16T>G and IVS6+36A>T (54%); -196A>C and -77G>A (49%); IVS2-59A>G and 240A>G (48%); -278C>T (31%); IVS4+27TCTI>D (29%); -144C>T and -588G>A (19%); 790C>T (16%); and other minor alleles with less than 5% frequency. Nineteen variations were used to characterize linkage disequilibrium (LD) structures at the CYP19A1 locus, which resulted in three LD blocks. Eight tagging SNPs in CYP19A1 were determined. Identification of CYP19A1 SNPs with LD blocks and tagging SNPs creates an important resource for genotype-phenotype association studies for estrogen-related phenotypes.