Microplastics and Forever Chemicals: Why Your Body Can't Detox Them — and What It Actually Needs — The genetic layer: why some people are sinks

Two people with identical exposure can have completely different trajectories. That&#8217;s not random. It&#8217;s toxicogenomic stratification. A few variants matter more than others: GSTM1 and GSTT1 null polymorphisms are complete deletions of two glutathione transferase genes. Present in 20&#8211;50% of the population depending on ethnicity. These individuals literally have no enzyme to conjugate glutathione to certain electrophiles &#8212; the reactive intermediates produced by phase I have nowhere to go. GSTP1 Ile105Val (rs1695) reduces activity against a different class of electrophiles, including those derived from polycyclic aromatic hydrocarbons and oxidized lipids. UGT1A1*28 , the Gilbert&#8217;s syndrome variant, cuts glucuronidation capacity by 30&#8211;40% in approximately 10% of people. Impaired glucuronidation affects BPA clearance, estrogen metabolism, bilirubin, and a large number of pharmaceuticals. MTHFR C677T and A1298C throttle the folate-methionine cycle, reducing SAMe production. Since SAMe is the methyl donor for COMT (which metabolizes catecholamines and estrogens), for methyltransferases that methylate phase II substrates, and for maintaining mitochondrial DNA integrity, MTHFR variants compound impairment across multiple systems simultaneously. PON1 Q192R, L55M, and C-108T variants determine paraoxonase activity, which handles oxidized lipids, organoph