rs1057126

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 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.