rs1799930

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 systematic review analyzed genetic associations with gastroschisis from 1980-2017, identifying 14 SNPs from 10 genes associated with crude risk and 30 SNPs from 14 genes with stratified risk. Four SNPs showed significant associations: rs4961 (ADD1, p=0.023), rs5443 (GNB3, p=0.002), rs1042713 (ADRB2, p=0.007), and rs1042714 (ADRB2, p=0.006). The findings suggest genetic susceptibility in gastroschisis is not restricted to gene-environment interactions, with blood pressure regulation genes playing a significant role in vascular disruption pathogenesis.

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 study examined PAH-related DNA adduct levels in 111 female never-smokers from Iran, evaluating 21 SNPs in 14 xenobiotic metabolism genes and 12 SNPs in 8 DNA repair genes. DNA adduct levels were significantly lower with NAT2 slow alleles (β=-0.24, p=0.01) and ERCC5 non-risk genotype (β=0.16, p=0.04), but higher with MPO risk alleles (β=0.21, p=0.01). The combination of phase I genes and measured NER capacity explained 17% more variation in adduct levels than environmental exposure alone (r²=0.24 vs 0.07), demonstrating the importance of genetic polymorphisms in PAH metabolism and DNA repair capacity.

Case-control study of 324 Japanese male workers examining genetic polymorphisms in xenobiotic-metabolizing enzymes (CYP2E1, NAT2, GSTM1, GSTT1, GSTP1, ALDH2, SOD2) and their association with multiple chemical sensitivity (MCS). SOD2 Val16Ala polymorphism (rs4880) showed significant association with high chemical sensitivity, with adjusted OR of 4.30 (95% CI 1.23-15.03) for Ala/Ala and Val/Ala genotypes versus Val/Val, and adjusted OR of 4.53 (95% CI 1.52-13.51) in additive genetic model analysis.

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).

This family-based association study examined genetic variation in xenobiotic metabolism genes and clubfoot risk. In 1,776 individuals from 619 families, rs1048943/CYP1A1 showed significant altered transmission (p=0.003), and CYP1A2 variants demonstrated both maternal (rs11854147, p=0.03, RR=1.24) and fetal (rs2470890, p=0.01, RR=1.33) genotypic effects. A significant gene interaction was detected between rs105740/EPHX1 and rs1799929/NAT2 (p=0.007). The authors conclude that xenobiotic metabolism genes may contribute to clubfoot susceptibility, particularly in the context of maternal smoking exposure.

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.