Association of genetic variations in aromatase gene with serum estrogen and estrogen/testosterone ratio in Chinese elderly men

Background: Single nucleotide polymorphism (SNP) rs2470152 of the gene CYP19A1 is associated with serum estradiol (E2) levels in Caucasian men. However, it remains to be verified if rs2470152 is the sole determinant accounting for the association. We determined whether 2 CYP19A1 SNPs tagging different haploblocks (rs2470152 and rs2899470) are associated with sex steroid levels in Chinese men. Method: Serum sex steroid level including E2, estrone (E1) and testosterone (T), of 1402 Chinese men aged ≥ 65 years were analyzed. Genotyping of the two CYP19A1 SNPs was performed using T_m-shift allele-specific PCR. Results: SNP rs2899470 was significantly associated with serum E2, E1 levels and E2/T ratio (p < 0.001). However, SNP rs2470152 was only modestly associated with E2/T ratio (p = 0.023). Analysis of haplotype showed a significant association between C-G, T-T haplotype with serum E2/T ratio (p = 0.019 and p = 1 × 10^{- 5}, respectively). Similarly, E2 levels was also associated the T-T and T-G haplotypes (p = 1 × 10^{- 5}). Conclusion: The genetic variation of CYP19A1 was associated with circulating estrogen levels in Chinese elderly men. In addition, it revealed that haplotype of rs2899470 and rs2470152, rather than rs2899470 alone, was a better indicator for the serum E2/T ratio and E2 levels.