Frequency of KLK3 gene deletions in the general population

Santi Rodriguez, Osama Alghamdi, Philip Guthrie, Hashem Shihab, Wendy McArdle, Tom Gaunt, Khalid K Alharbi, Ian Day

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One of the kallikrein genes (KLK3) encodes prostate-specific antigen, a key biomarker for prostate cancer. A number of factors, both genetic and non-genetic, determine variation of serum prostate-specific antigen concentrations in the population. We have recently found three KLK3 deletions in individuals with very low prostate-specific antigen concentrations, suggesting a link between abnormally reduced KLK3 expression and deletions of KLK3. Here, we aim to determine the frequency of kallikrein gene 3 deletions in the general population.


The frequency of KLK3 deletions in the general population was estimated from the 1958 Birth Cohort sample (n = 3815) using amplification ratiometry control system. In silico analyses using PennCNV were carried out in the same cohort and in NBS-WTCCC2 in order to provide an independent estimation of the frequency of KLK3 deletions in the general population.


Amplification ratiometry control system results from the 1958 cohort indicated a frequency of KLK3 deletions of 0.81% (3.98% following a less stringent calling criterion). From in silico analyses, we found that potential deletions harbouring the KLK3 gene occurred at rates of 2.13% (1958 Cohort, n = 2867) and 0.99% (NBS-WTCCC2, n = 2737), respectively. These results are in good agreement with our in vitro experiments. All deletions found were in heterozygosis.


We conclude that a number of individuals from the general population present KLK3 deletions in heterozygosis. Further studies are required in order to know if interpretation of low serum prostate-specific antigen concentrations in individuals with KLK3 deletions may offer false-negative assurances with consequences for prostate cancer screening, diagnosis and monitoring
Original languageEnglish
Pages (from-to)472-480
Number of pages9
JournalAnnals of Clinical Biochemistry
Issue number4
Early online date23 Aug 2016
Publication statusPublished - 1 Jul 2017


  • KLK3
  • prostate-specific antigen
  • amplification ratiometry control system
  • PennCNV
  • deletions

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