Dataset Information

Genetic variation in KLK2 and KLK3 is associated with concentrations of hK2 and PSA in serum and seminal plasma in young men.

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 < 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.

SUBMITTER: Savblom C

PROVIDER: S-EPMC3943614 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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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 C Halldén Christer C Cronin Angel M AM Säll Torbjörn T Savage Caroline C Vertosick Emily A EA Klein Robert J RJ Giwercman Aleksander A Lilja Hans H

Clinical chemistry 20131122 3

<h4>Background</h4>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 concent ...[more]

PMID: 24270797

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Project description:BackgroundEpidemiologic literature on the relation of organochlorine pesticides (OCPs) with semen quality among adult men has been inconclusive, and no studies have prospectively explored the association between peripubertal serum OCPs and semen parameters in young men.ObjectiveTo evaluate prospective associations of peripubertal serum concentrations of hexachlorobenzene (HCB), β-hexachlorocylohexane (β-HCH), and p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) with semen parameters among young Russian men.MethodsThis prospective cohort study included 152 young men who enrolled in the Russian Children's Study (2003-2005) at age 8-9 years and were followed annually until young adulthood. HCB, β-HCH, and p,p'-DDE concentrations were measured at the CDC by mass spectrometry in serum collected at enrollment. Between 18 and 23 years, semen samples (n = 298) were provided for analysis of volume, concentration, and progressive motility; we also calculated total sperm count and total progressive motile count. Linear mixed models were used to examine the longitudinal associations of quartiles of serum HCB, β-HCH and p,p'-DDE with semen parameters, adjusting for total serum lipids, body mass index, smoking, abstinence time and baseline dietary macronutrient intake.ResultsLipid-adjusted medians (IQR) for serum HCB, βHCH and p,ṕ-DDE, respectively, were 150 ng/g lipid (102-243), 172 ng/g lipid (120-257) and 275 ng/g lipid (190-465). In adjusted models, we observed lower ejaculated volume with higher serum concentrations of HCB and βHCH, along with reduced progressive motility with higher concentrations of βHCH andp,ṕ-DDE. Men in the highest quartile of serum HCB had a mean (95% Confidence Interval, CI) ejaculated volume of 2.25 mL (1.89, 2.60), as compared to those in the lowest quartile with a mean (95% CI) of 2.97 mL (2.46, 3.49) (p = 0.03). Also, men in the highest quartile of serum p,ṕ-DDE had a mean (95% CI) progressive motility of 51.1% (48.6, 53.7), as compared to those in the lowest quartile with a mean (95% CI) of 55.1% (51.7, 58.5) (p = 0.07).ConclusionIn this longitudinal Russian cohort study, peripubertal serum concentrations of selected OCPs were associated with lower ejaculated volume and progressive motility highlighting the importance of the peripubertal window when evaluating chemical exposures in relation to semen quality.

Project description:Background:Previous studies indicated that serum 25-hydroxyvitamin D [25(OH)D] concentrations are positively associated with physical activity levels independent of sun exposure. However, the effect of resistance training on serum 25(OH) D concentrations remains unclear. Thus, this study aimed to examine the effect of chronic resistance training on serum 25(OH) D concentrations and determine whether 25(OH) D concentration variations are influenced by body composition changes. Methods:Eighteen young men aged 19-39?years were randomly divided into a 12-week resistance training group (RT, n?=?9) and non-exercise control group (CON, n?=?9). The trial was undertaken in Shanghai University of Sport in Shanghai, China. Randomization and allocation to trial group were carried out by a central computer system. Serum 25(OH) D and intact parathyroid hormone concentrations were measured using commercially available enzyme-linked immunosorbent assay kits. Body composition was measured by dual-energy X-ray absorptiometry. Results:The average serum 25(OH) D concentrations were 26.6?nmol/L at baseline. After the 12-week intervention program, serum 25(OH) D concentrations significantly increased in both groups. Serum 25(OH) D concentrations at midpoint (6-week) increased significantly only in the CON group (P?<?0.01). From training midpoint to endpoint, a significantly greater increase in serum 25(OH) D concentrations was noted in the RT group (P-interaction?=?0.043); 25(OH) D concentration changes (end-pre) were negatively related to fat-free mass (mid-pre) (r?=?-?0.565, P?=?0.015) and muscle mass (mid-pre) (r?=?-?0.554, P?=?0.017). Conclusions:There were no beneficial effects of the 12-week resistance training on serum 25(OH) D concentration in vitamin D deficient young men, and an indication that seasonal increase in serum 25(OH) D concentrations during the early phase of resistance training was transiently inhibited, which may partly be attributed to resistance training-induced muscle mass gain. Trial registration:Chinese Clinical Trial Registry, ChiCTR2000030876. Registered 16 March 2020 - Retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=50504.

Dataset Information

Genetic variation in KLK2 and KLK3 is associated with concentrations of hK2 and PSA in serum and seminal plasma in young men.

Publications

Genetic variation in KLK2 and KLK3 is associated with concentrations of hK2 and PSA in serum and seminal plasma in young men.

Similar Datasets

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