Influence of COMT genotype polymorphism on plasma and urine green tea catechin levels in postmenopausal women

Abstract

Catechins are the major polyphenolic compound in green tea that have been investigated extensively over the past few decades in relation to the treatment of various chronic diseases including diabetes, cardiovascular disease, and cancer. O-methylation is a major Phase II metabolic pathway of green tea catechins (GTCs) via the enzyme catechol-O-methyltransferase (COMT). A single nucleotide polymorphism in the gene coding for COMT leads to individuals with a high-, intermediate-, or low-activity COMT enzyme. An epidemiological case-control study suggests that green tea consumption is associated with reduced risk of breast cancer in women with an intermediate- or low-activity COMT genotype. A cross-sectional analysis discovered that men homozygous for the low-activity COMT genotype showed a reduction in total tea polyphenols in spot urine samples compared to the intermediate- and high-activity genotypes. Several human intervention trials have assessed green tea intake, metabolism, and COMT genotype with conflicting results. The aim of the present study was to determine if the COMT polymorphism would modify the excretion and plasma levels of GTCs in 180 postmenopausal women at high risk for breast cancer consuming a green tea extract supplement containing 1222 mg total catechins daily for 12 months. All participants in the study were a sub-set from the larger parent study "Green Tea and Reduction of Breast Cancer Risk." Thirty subjects with the high-activity COMT genotype, thirty with intermediate-activity COMT genotype, and thirty with low-activity COMT genotype from each of the placebo and treatment groups were analyzed. No statistically significant differences were found in any urinary or plasma catechin metabolite measurements between the homozygous high-activity and homozygous low-activity COMT genotype in the treatment group. Additionally, no differences were found when high-, intermediate-, and low-activity COMT genotypes were all compared in the treatment group. This suggests that the COMT genotype does not play a major role in GTC metabolism. Dosing of GTC and timing of biological samples are important factors that may need further research in future trials evaluating the effect of COMT genotype and GTC metabolism.