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Genetic Variation in KLK2 and KLK3 Is Associated with Concentrations of hK2 and PSA in Serum and Seminal Plasma in Young Men

Sävblom, Charlotta LU ; Halldén, Christer LU ; Cronin, Angel M.; Säll, Torbjörn LU ; Savage, Caroline; Vertosick, Emily A.; Klein, Robert J.; Giwercman, Aleksander LU and Lilja, Hans LU (2014) In Clinical Chemistry 60(3). p.490-499
Abstract
BACKGROUND: Genetic variants in KLK2 and KLK3 have been associated with increased serum concentrations of their encoded proteins, human kallikrein-related peptidase 2 (hK2) and prostate-specific antigen (PSA), and with prostate cancer in older men. Low PSA concentrations in seminal plasma (SP) have been associated with low sperm motility. To evaluate whether KLK2 and KLK3 genetic variants affect physiological prostatic secretion, we studied the association of SNPs with hK2 and PSA concentrations in SP and serum of young, healthy men. METHODS: Leukocyte DNA was extracted from 303 male military conscripts (median age 18.1 years). Nine SNPs across KLK2-KLK3 were genotyped. We measured PSA and hK2 in SP and serum using immunofluorometric... (More)
BACKGROUND: Genetic variants in KLK2 and KLK3 have been associated with increased serum concentrations of their encoded proteins, human kallikrein-related peptidase 2 (hK2) and prostate-specific antigen (PSA), and with prostate cancer in older men. Low PSA concentrations in seminal plasma (SP) have been associated with low sperm motility. To evaluate whether KLK2 and KLK3 genetic variants affect physiological prostatic secretion, we studied the association of SNPs with hK2 and PSA concentrations in SP and serum of young, healthy men. METHODS: Leukocyte DNA was extracted from 303 male military conscripts (median age 18.1 years). Nine SNPs across KLK2-KLK3 were genotyped. We measured PSA and hK2 in SP and serum using immunofluorometric assays. The association of genotype frequencies with hK2 and PSA concentrations was tested with the Kruskal-Wallis test. RESULTS: Four KLK2 SNPs (rs198972, rs198977, rs198978, and rs80050017) were strongly associated with hK2 concentrations in SP and serum, with individuals homozygous for the major alleles having 3-to 7-fold higher concentrations than the intermediate concentrations found in other homozygotes and heterozygotes (all P < 0.001). Three of these SNPs were significantly associated with percentage of free PSA (% fPSA) in serum (all P < 0.007). Three KLK3 SNPs showed associations with PSA in SP, and the rs1058205 SNP was associated with total PSA in serum (P = 0.001) and % fPSA (P = 0.015). CONCLUSIONS: Associations observed in young, healthy men between the SP and serum concentrations of hK2 and PSA and several genetic variants in KLK2 and KLK3 could be useful to refine models of PSA cutoff values in prostate cancer testing. (C) 2013 American Association for Clinical Chemistry (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Clinical Chemistry
volume
60
issue
3
pages
490 - 499
publisher
American Association for Clinical Chemistry
external identifiers
  • wos:000335146800013
  • scopus:84895812834
ISSN
0009-9147
DOI
10.1373/clinchem.2013.211219
language
English
LU publication?
yes
id
becebe82-624d-4d08-83f3-18e3fc1ee149 (old id 4487446)
date added to LUP
2014-07-01 07:32:43
date last changed
2017-10-01 03:10:38
@article{becebe82-624d-4d08-83f3-18e3fc1ee149,
  abstract     = {BACKGROUND: Genetic variants in KLK2 and KLK3 have been associated with increased serum concentrations of their encoded proteins, human kallikrein-related peptidase 2 (hK2) and prostate-specific antigen (PSA), and with prostate cancer in older men. Low PSA concentrations in seminal plasma (SP) have been associated with low sperm motility. To evaluate whether KLK2 and KLK3 genetic variants affect physiological prostatic secretion, we studied the association of SNPs with hK2 and PSA concentrations in SP and serum of young, healthy men. METHODS: Leukocyte DNA was extracted from 303 male military conscripts (median age 18.1 years). Nine SNPs across KLK2-KLK3 were genotyped. We measured PSA and hK2 in SP and serum using immunofluorometric assays. The association of genotype frequencies with hK2 and PSA concentrations was tested with the Kruskal-Wallis test. RESULTS: Four KLK2 SNPs (rs198972, rs198977, rs198978, and rs80050017) were strongly associated with hK2 concentrations in SP and serum, with individuals homozygous for the major alleles having 3-to 7-fold higher concentrations than the intermediate concentrations found in other homozygotes and heterozygotes (all P &lt; 0.001). Three of these SNPs were significantly associated with percentage of free PSA (% fPSA) in serum (all P &lt; 0.007). Three KLK3 SNPs showed associations with PSA in SP, and the rs1058205 SNP was associated with total PSA in serum (P = 0.001) and % fPSA (P = 0.015). CONCLUSIONS: Associations observed in young, healthy men between the SP and serum concentrations of hK2 and PSA and several genetic variants in KLK2 and KLK3 could be useful to refine models of PSA cutoff values in prostate cancer testing. (C) 2013 American Association for Clinical Chemistry},
  author       = {Sävblom, Charlotta and Halldén, Christer and Cronin, Angel M. and Säll, Torbjörn and Savage, Caroline and Vertosick, Emily A. and Klein, Robert J. and Giwercman, Aleksander and Lilja, Hans},
  issn         = {0009-9147},
  language     = {eng},
  number       = {3},
  pages        = {490--499},
  publisher    = {American Association for Clinical Chemistry},
  series       = {Clinical Chemistry},
  title        = {Genetic Variation in KLK2 and KLK3 Is Associated with Concentrations of hK2 and PSA in Serum and Seminal Plasma in Young Men},
  url          = {http://dx.doi.org/10.1373/clinchem.2013.211219},
  volume       = {60},
  year         = {2014},
}