rs1801280

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 in 100 Russian vitiligo patients and 100 controls identified a strong novel association between GSTP1 rs1138272 (Ala114Val, OR=13.03, Bonferroni-adjusted P=0.0015) and vitiligo susceptibility. Cumulative analysis of multiple xenobiotic metabolizing genes showed that carrying higher numbers of risk alleles was associated with increased vitiligo risk (9-16 vs 3-8 alleles: OR=2.79, P=0.00063), supporting a polygenic model for vitiligo involving detoxification pathway genes.

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.

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.

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.