Metformin

The gene behind this variant is better known for something else entirely — ATM is the ataxia telangiectasia gene, central to DNA repair and cell cycle control. Here, a common variant near it (rs11212617) predicts who responds better to metformin: found in 1,024 Scottish patients, replicated in nearly 3,000 more across two cohorts, with an odds ratio of 1.35 for treatment success. This is not a guess at a mechanism — in a follow-up cell experiment, blocking ATM blunted metformin's activation of AMPK, the enzyme metformin is known to work through, placing ATM upstream in that pathway. Metformin stays first-line regardless of genotype; this is about how well it is likely to work, not whether to prescribe it.

Zhou K et al. (GoDARTS/UKPDS/MAGIC investigators), Nature Genetics 2011 — common variants near ATM and glycemic response to metformin, with cell-line mechanistic follow-up. PMID:21186350

SLC2A2 encodes GLUT2, the glucose transporter metformin's target tissue depends on. A common intronic variant (rs8192675) predicted a modestly greater HbA1c reduction from metformin across 10,577 people of European ancestry, and separately turned out to be the strongest known predictor of how much SLC2A2 gets expressed in the liver — a real mechanistic link, not just a statistical one. In obese patients specifically, the effect grew to roughly half of what adding a second drug (a DPP-4 inhibitor) would achieve. The study's own framing is "a potential biomarker for stratified medicine" — a real, mechanistically grounded lead, not yet something a guideline tells a clinician to act on.

Zhou K et al. (MetGen Consortium), Nature Genetics 2016 — SLC2A2 variation and glycemic response to metformin, with liver eQTL evidence. PMID:27500523