Mexican and Indigenous rheumatology PGx priors may be miscalibrated

After years on the clinic floor in Mexico, the same pattern keeps recurring: standard methotrexate, sulfasalazine, hydroxychloroquine, and allopurinol regimens do not always produce the toxicity and response patterns that the published literature would lead you to expect in Mexican mestizo and Indigenous patients.

Working hypothesis:

1. Most pharmacogenomic priors currently used in rheumatology were trained on predominantly European cohorts.
2. Variant frequencies in genes relevant to methotrexate and adjacent rheumatology drugs, including MTHFR, HLA-B, CYP2C9, VKORC1, and TPMT, differ across Mexican mestizo and Indigenous populations.
3. Those differences may help explain the response and toxicity patterns observed in clinic.

A targeted, population-specific pharmacogenomic panel, extractable from saliva at point-of-care, might predict methotrexate response and toxicity, plus selected adjacent rheumatology drug risks, better than European-trained priors currently embedded in routine practice.

This is a falsifiable claim: if a locked, prospective panel does not improve calibration or clinical utility over the baseline model, the hypothesis should be discarded or redesigned.