In Response: We wish to acknowledge the outstanding and careful work done by Prof. Milanese in assessing the functionality of 5 ¶ untranslated region (UTR) single nucleotide polymorphisms (SNP) in the DEFB1 gene and are gratified that they agree with our assessment that these SNPs can modulate gene expression. There are some differences in the experimental models used by the Milanese laboratory and our laboratory that could account for the differences found in the correlation between specific

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... Ps and gene expression. In their analysis, the À44G mutation reduces gene expression, whereas in our laboratory, the À44G mutation correlated with increased gene expression. It is important to point out that our 5 ¶ UTR DNAs were not generated by PCR (as the ones reported by Prof. Milanese were) but were cloned from actual cell lines. As such, our À44G mutant fragment also contained the À20G mutation. This cloned (and sequence verified) 433-bp fragment containing both the À44 and the À20 base alterations enhances reporter expression in both the DU-145 and the TSU-Pr1 cell lines when compared with cloned fragments containing only the À20G mutation. This result has been repeated and verified by us multiple times. Thus, we agree that the functionality of DEFB1 5 ¶ UTR SNPs continues to require additional study and that the functionality of a specific base change may be modified by additional changes found in the near neighboring area of the gene. The cell line used to assay promoter-reporter function may also modify specific experimental results.