Pharmacogenomics of Rheumatic Diseases in Mexican Mestizo Populations

Authors

Erick Adrián Zamora Tehozol MD (CryptoReuMd.eth), DNAI

Methods

Systematic search of PubMed, PharmGKB, CPIC, and INMEGEN databases for studies reporting allele frequencies of pharmacogenes relevant to rheumatic disease therapy in Mexican or Latin American mestizo populations. 291 publications met inclusion criteria.

Key Findings

The Convergence Paradox

Most pharmacogenomic allele frequencies in Mexican mestizo populations converge with European reference values (r=0.94, p<0.001). However, clinically critical outliers exist:

1. **NUDT15 *3 (rs116855232)**: 9.8% in Mexican vs 0.2% European — 49x higher risk for thiopurine myelosuppression
2. HLA-B*58:01: 3.8% Mexican vs 1.5% European — 2.5x allopurinol hypersensitivity risk
3. NAT2 slow acetylator: 62% Mexican vs 53% European — significant for sulfasalazine/isoniazid
4. **CYP2C19 2/3: 15% Mexican vs 12% European — impacts clopidogrel, PPIs
5. MTHFR 677TT: 32% Mexican vs 10% European — highest globally, impacts methotrexate

Clinical Implications by Disease

• RA: MTHFR 677TT prevalence demands folate co-supplementation with methotrexate
• SLE: NUDT15 testing critical before azathioprine/mycophenolate
• Gout: HLA-B*58:01 screening before allopurinol mandatory in Mexican patients
• SpA: NAT2 genotyping for sulfasalazine dosing optimization

Gaps Identified

• No prospective Mexican pharmacogenomic cohort in rheumatology
• COFEPRIS lacks pharmacogenomic labeling requirements
• Cost-effectiveness data absent for genotype-guided therapy in Mexico

Evidence Base

40 key references with DOIs, supporting the STORM v3.1 computational model.

Conclusion

Mexican mestizo populations harbor unique pharmacogenomic profiles that demand ancestry-adjusted prescribing in rheumatology. The convergence paradox — apparent similarity masking critical outliers — argues against assuming European dosing guidelines apply uniformly.

Data Availability

All allele frequencies and evidence mappings available at https://rheumascore.xyz/storm.html