Effect of homeodomain protein NKX3.1 R52C polymorphism on prostate gland size

ObjectivesTo determine the association between prostatic enlargement and a cytosine for thymine genetic polymorphism at nucleotide 154 (C154T) of the NKX3.1 prostate homeobox gene. The polymorphism, found in 10% of the population, affects the NKX3.l protein by replacing a cysteine for arginine at amino acid 52 and alters protein phosphorylation and DNA binding.MethodsA study group of men without prostate cancer from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial was identified who had had at least three annual serial digital rectal examinations by a single examiner. The cohort of 772 men consisted of the lowest and highest tertiles of the entire study group as defined by two-dimensional measurements at digital rectal examination. The TaqMan allelic discrimination assay was used to genotype NKX3.1 for the nucleotide 154 polymorphism.ResultsThe men in the lower tertile (n = 413) had a mean age of 60.8 years, mean prostate-specific antigen level of 1.2 ng/mL, and mean prostate volume of 37.9 ± 4.5 cm3. The men in the upper tertile (n = 359) had a mean age of 61.6 years, mean prostate-specific antigen level of 2.1 ng/mL, and mean prostate volume of 61 ± 6.3 cm3. The men in the upper tertile had a greater likelihood of having a clinical history of benign prostatic hyperplasia and more frequent nocturia. The presence of one or two polymorphic NKX3.1 alleles conferred a risk of 1.6 (95% confidence interval 1.0 to 2.6) for an enlarged prostate (highest tertile).ConclusionsThe NKX3.1 nucleotide 154 C/T or T/T genotype increases the relative odds for prostatic enlargement. The group with prostatic enlargement also had increased clinical benign prostatic hyperplasia and nocturia.