rs15561

A prospective study of 91 primary central nervous system lymphoma (PCNSL) patients examined genetic polymorphisms in DNA repair, one-carbon metabolism, and metabolism genes as prognostic markers. ABCB1 rs1045642 was identified as an independent prognostic factor, with the CC genotype significantly associated with shorter progression-free survival (PFS: 16 months CC vs. 27 months TT/CT, HR=1.9, P=0.036) and higher risk of disease progression compared to T allele carriers.

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 methods paper demonstrates that single-nucleotide mismatches in primers located close to target SNPs cause preferential amplification of one haplotype strand, leading to misgenotyping of heterozygotes as homozygotes in PCR and sequencing-based genotyping. The study examined NAT1 (rs1057126, rs15561) and TP53 (rs12947788, rs12951053) loci, showing misgenotyping reaches 100% when mismatches are at the 3rd nucleotide position from the 3' primer end, but decreases significantly as mismatch position shifts toward the 5' end.

This functional study investigated the effects of NAT1 (N-acetyltransferase 1) genetic polymorphisms in the coding region and 3'-UTR on enzyme activity, mRNA, and protein levels using recombinant expression in COS-1 cells. The 1088T>A (rs1057126) and 1095C>A (rs15561) variants slightly reduced NAT1 catalytic activity and expression levels. A 9-base pair deletion in the 3'-UTR reduced activity, while the 445G>A (rs4987076), 459G>A (rs4986990), and 640T>G (rs4986783) coding region haplotype increased activity. These findings provide biological support for previously reported associations of 1088T>A and 1095C>A polymorphisms with birth defects including oral clefts and limb deficiency.