TSER 3R G to C Single Nucleotide Polymorphism SNP

In a recent study, Mandola et al. showed that the 28 bp TSER tandem repeats contain elements that bind upstream stimulating factor (USF), and also that ligand binding by USF-1 and USF-2 enhances the transcriptional activity of the TS gene (Fig. 2) (42). Electrophoretic mobility shift analysis has shown that the presence of a G-to-C single nucleotide polymorphism (SNP) within the second repeat of the 3R allele leads to decreased ability of upstream stimulatory factor (USF) to bind within the repeat and therefore sequentially result in decreased transcriptional activity of the 3R TS gene variant (42).

The authors demonstrated that these polymorphisms alter mRNA stability and therefore enzyme activity. They showed that whereas phosphorylated USF-1 bound the normal consensus sequence, the G-to-C substitution abolished the binding (42,59). In vitro transcription analysis showed that the TSER 3RC allele caused a lower transcription rate than the TSER 3RG variant, which was comparable to the TSER 2R genotype. Interestingly, the frequency of the 3RC allele among all 3R alleles showed a variation of 56%, 47%, 28%, and 37% for Whites, Hispanics, African-Americans, and Singapore and Chinese, respectively. Although the overall frequency was similar to that reported by Mandola et al., Japanese females were noted to have lower frequency of the 3RG allele than males (60).

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