rs1208

Systematic review of worldwide genetic diversity of the NAT2 gene across 60,888 individuals from 122 populations in 51 countries. Analyzed eight NAT2 polymorphisms (rs1801279, rs1041983, rs1801280, rs1799929, rs1799930, rs1208, rs1799931, rs1495741) to characterize acetylation phenotypes globally. Slow phenotype most common worldwide (frequency 0.44), especially in African, European, and Middle Eastern populations (0.48-0.79), while rapid phenotype predominates in East Asians and Native Americans (0.25-0.53). Compiled data from 160 publications including 115 case-control studies to map NAT2 diversity patterns associated with metabolism of drugs and heterocyclic aromatic amines.

This study determined NAT2 (N-acetyltransferase 2) acetylation status in 1,556 Greenlandic individuals using SNP panels and genotype imputation. The fraction of slow acetylators was 17.5% overall but varied significantly by Inuit ancestry (12.2% with >70% Inuit ancestry vs 25.6% with <50% Inuit ancestry). Different SNP panels showed high concordance (2-SNP and 4-SNP panels achieved 100% agreement with the 7-SNP reference panel), demonstrating reliable NAT2 status assessment. These findings support pharmacogenetics-based isoniazid dosing for tuberculosis treatment in Greenland.

A candidate gene association study of 265 elderly Caucasian volunteers from the UK found no significant associations between NAT2 or APOE gene polymorphisms and age-related hearing loss (ARHL) using haplotype tagging SNP analysis. Linear regression analysis of 13 NAT2 htSNPs (including rs1799930/NAT2*6A) and APOE ε4 allele presence showed no significant associations (P > 0.05) with three hearing phenotypes (severity, slope, concavity), and epistasis analysis revealed no gene-gene interaction between these loci.

This case-control study examined gene-environment interactions between smoking and drug-metabolizing enzyme (DME) polymorphisms in rheumatoid arthritis (RA) risk among 727 African American RA cases and 268 controls. While no individual DME genotypes were significantly associated with RA, significant additive interactions were found between heavy smoking (≥10 pack-years) and NAT2 SNPs rs9987109 (P_add=0.000003) and rs1208 (P_add=0.00001), with attributable proportions ranging from 0.61-0.67. The NAT2 rs1208 haplotype was associated with a 4.15-fold increased RA risk in heavy smokers (p=0.005).

Study of 314 German workers (218 bitumen-exposed, 96 non-exposed controls) examining how 18 SNPs in metabolizing enzyme genes modulate urinary PAH metabolites (1-OHP and OHPHE). The CYP1A1 3801T>C CC variant showed 58% higher OHPHE (P=0.051), GSTM1*1 carriers had 11% lower OHPHE (P=0.046), and NAT2*803GG showed 15-16% decrease in OHPHE (P=0.042). No SNPs reached significance for 1-OHP.