rs1495741

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 of 231 bladder urothelial carcinoma (UC) patients and 261 benign controls found that rs9642880[T] and rs798766[T] variants increase bladder-UC risk (OR=1.72, p=0.028 and OR=1.84, p=0.01 respectively), but unlike upper tract UC, these variants are not associated with disease aggressiveness (grade or stage). The findings highlight distinct genetic differences between bladder-UC and upper urinary tract urothelial carcinoma.

A case-control validation study of 1,450 cases and 1,725 controls from Germany, Hungary, Venezuela, and Pakistan investigated the association of rs2854744 in the IGFBP3 gene with urinary bladder cancer risk. The study found no significant association (P = 0.6510 adjusted for age, gender, and smoking; OR = 1.07, 95% CI 0.86-1.34), failing to confirm the previously published association by Safarinejad et al. A meta-analysis including all available case-control series resulted in an OR of 1.00 (P = 0.9562), indicating no effect of the [A] allele.