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ERS1

The ESR1 gene regulates estrogen receptor alpha activity which is involved in hormone binding and activation and also regulates gene transcription. ESR1 is thought to enhance the effect of estrogen that attaches to it. This is necessary for estrogen to perform its functions in the body but can be negative if high amounts of very strong forms of estrogen (e.g. E2 and 4OH) are dominant in circulation. Variants in ESR1 are associated with enhanced receptor activity.

The CC allele indicates normal (not increased) ESR1 activity. High estrogen levels will increase the risk of estrogen-linked conditions regardless of genotype. Optimising phase II estrogen elimination via methylation (COMT), sulphation (SULT) and glucuronidation (UGT) pathways will support healthy estrogen levels. Encouraging CYP1A1 activity over CYP1B1 and CYP3A4 will also ensure that 'weaker' 2OH is dominant in circulation over the 'stronger' 4OH and 16aOH forms.

The TC allele shows moderately increased ESR1 activity. This genotype increases the risk of estrogen-linked conditions particularly if 4OH and 16OH estrogen are dominant in circulation. Care should be taken to reduce circulating estrogen by improving phase II inactivation pathways - methylation (COMT), sulphation (SULT) and glucuronidation (UGT), encouraging phase I CYP1A1 activity over CYP1B1 and CYP3A4 to ensure that 'weaker' 2OH estrogen is dominant in circulation.

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