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In addition, rs61752561 in KLK3 showed an association with hK2 amount and concentration in seminal plasma, but has a low minor allele frequency (MAF) of only 0.
The genotypes of all 3 KLK3 SNPs (rs2271094, rs61752561, and rs1058205) were associated with PSA amount or concentration in seminal plasma (Table 3).
Our hypothesis is that very low serum PSA concentrations may reflect inactivating gene mutations or gross genetic rearrangements involving KLK3.
We sequenced all exons and the regulatory region of KLK3 to search for genetic defects in KLK3 that would lead to abnormal PSA concentrations.
Interestingly, the KLK3 variant (rs2735839) was associated only with increased prostate cancer risk during the PSA era, but no era effect was observed for the other variants.
6] Human genes: KLK8, kallikrein-related peptidase 8; KLK3, kallikrein-related peptidase 3; KLK5, kallikrein-related peptidase 5; KLK6, kallikrein-related peptidase 6; KLK7, kallikrein-related peptidase 7; KLK10, kallikrein-related peptidase 10; KLK11, kallikrein-related peptidase 11; KLK13, kallikrein-related peptidase 13; KLK14, kallikrein-related peptidase 14; ERBB4, v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian); LOX, lysyl oxidase.
For that purpose, we measured miR-155, miR-200c, and CDH16, PPIA, and TBP expression in samples of nonmalignant renal tissue after radical nephrectomy and measured miR-130b, miR205, and HIF1A, KLK3, and HPRT1 expression in nonmalignant samples of prostate tissue after radical prostatectomy (Fig.
KLK2 and KLK3 are highly abundant in the prostate and found in seminal plasma, as expected.
Gene Localization annotation prediction SwissProt localization Tissue specificity KLK3 (PSA) Secreted Secreted protein Primarily prostate ACPP Secreted No annotation Primarily prostate VEGF Secreted Secreted protein Ubiquitous FN1 Secreted Secreted protein Ubiquitous ZWINT Not secreted Nucleus Moderatea AMACR Not secreted Peroxisome mitochondrion Ubiquitous HPN Not secreted Type II membrane Moderatea We analyzed 7 genes by the secretion and specificity prediction methods described above.
6] Human genes: KLKI, kallikrein 1, renal/pancreas/salivary; KLK2, kallikrein 2, prostatic; KLK3, kallikrein 3 (prostate-specific antigen); and KLK4, kallikrein 4 (prostase, enamel matrix, prostate).
4] Human genes: PCA3, prostate cancer gene 3; KLK3, kallikrein 3 (prostate-specific antigen).
Among human kallikrein splice variants reported to date, two of them, Psa-rp2 for the KLK3 gene (GenBank accession no.