The Kallikrein-Related Peptidases hK2 and PSA with Emphasis on Genetic Variation, Secretion, and Sperm Motility
Författare
Summary, in English
The present objective was to evaluate factors that might influence release of hK2 and PSA, and to study those two proteins with regard to their levels in seminal plasma and blood, and their association with sperm motility in young healthy men without prostate disease.
PSA and hK2 were measured by immunofluorometric assay. Genomic DNA was prepared from peripheral leukocytes, and genotyping was performed with the Sequenom Mass Array System. Levels of hK2 and PSA were found to be associated with variants in the genes encoding hK2 (KLK2) and PSA (KLK3) in young men (mean age 18 years). The single-nucleotide polymorphisms (SNPs) rs198972, rs198977, rs198978, and “SNP2” in KLK2 were associated with lower hK2 levels in seminal plasma and serum in carriers of the TT genotype. In KLK3, the AA genotype in rs266882 in combination with CAG > 22 were correlated with higher total PSA (tPSA) in serum; rs2271094 and “SNP1" were associated with lower tPSA concentrations in seminal plasma from subjects homozygous for the common allele (A or G, respectively). Carriers of the common T allele in rs1058205 in KLK3, had higher amounts of tPSA in seminal plasma, higher concentrations of tPSA in serum, and a lower ratio of free to tPSA (%fPSA). Free PSA (fPSA) in blood showed ~17% co-variation with PSA in semen, whereas no relationship was found between levels of complexed PSA (cPSA) in blood and PSA in semen. In blood, levels of cPSA, but not fPSA, increased with age, which may reflect an increasing incidence of prostate disease. In men 19–40 years, an age when reproduction most commonly takes place, correlations were found between hK2 and PSA in seminal plasma (p < 0.001, r = 0.47) and between hK2 and age (p = 0.01, r = –0.20). Men in that age group who were in the lowest quartile with respect to amount of PSA in seminal plasma, semen volume, and zinc concentration had, respectively, 5.8%, 4.1%, and 3.9% fewer progressively motile sperm. These findings suggest that a decrease in secretory function of the prostate can impair sperm motility. The present results obtained by analysing the allelic variants of KLK2 and KLK3 might be useful for refining models of PSA cut-off values in PCa testing.
Avdelning/ar
Publiceringsår
2008
Språk
Engelska
Publikation/Tidskrift/Serie
Faculty of Medicine Doctoral Dissertation Series
Volym
2008:47
Fulltext
Dokumenttyp
Doktorsavhandling
Förlag
Lund University
Ämne
- Medicinal Chemistry
Nyckelord
- human glandular kallikrein 2
- KLK3
- hk2
- prostate-specific antigen
- PSA
- sperm motility
- seminal plasma
- androgen receptor
- SNP
- CAG
- KLK2
Status
Published
Forskningsgrupp
- Clinical Chemistry, Malmö
Handledare
ISBN/ISSN/Övrigt
- ISSN: 1652-8220
- ISBN: 978-91-86059-00-2
Försvarsdatum
10 maj 2008
Försvarstid
10:00
Försvarsplats
CRC Lecture Hall, CRC, Malmö University Hospital, Malmö
Opponent
- Mika Matikainen (Associate Professor)