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Association of Haplotypes in Exon 4 of KLK2 Gene with Raised serum Prostate-specific Antigen

American Journal of Molecular Biology 2023年第1期13卷 57-66页

作者： Innocent s. I. Ogbu Ogochukwu A. Nwankwo chinemere C. Ogbu Emmanuel Nna Kingsley K. Anya Malachy O. Odoh David C. Obasi Department of Medical Laboratory science Enugu Campus University of Nigeria Enugu Nigeria Department of Medical Laboratory science Evangel University Akaeze Nigeria safety Molecular Pathology Laboratory Enugu Nigeria Department of Medical Laboratory science Ebonyi State University Abakaliki Nigeria Department of Biochemistry Evangel University Akaeze Nigeria

The standard diagnostic modalities for Prostate Cancer (PC) include serum Prostate-specific Antigen (PsA) assay, Digital Rectal Examination (DRE), and histological examination of prostate biopsy. They are limited by low predictive potential and inability to predict which patients are at risk of developing metastatic disease. The aim of this study is to investigate the exon 4 of the KLK2 gene of subjects for changes in its nucleotide sequences (sNPs) and determine the correlation of these changes with serum PsA in an Igbo population of Nigeria. One hundred male subjects aged 40 years and above, who gave their consent, were used for the study. Their PsA determinations were done using ELIsA technique while genetic studies were carried out using real-time PCR. tPsA, fPsA, and % fPsA of the subjects ranged between 0.8% - 18.30%, 0.10% - 1.60% and 0.0% - 0.7% respectively. Of the 100 subjects, 28 subjects had tPsA levels above 4.0 ng/ml with a mean of 7.10 (±3.30) ng/ml. Those with tPsA less than 4 ng/ml had a mean of 1.87 (±0.85) ng/m. 15 subjects showed sNPs with a mean tPsA of 6.87 (±4.82) ng/ml while the remaining 85 subjects without sNPs had a mean of 1.86 (±0.80) ng/ml. Results from direct DNA sequencing showed 11 sNPs. Ten subjects are curated in sNP database while one is uncurated. The chi-square test showed significant association (p = 0.00) between tPsA levels and sNPs mutation (Xsup>2sup> = 17.35, p = 0.00). A Kruskal-Wallis test demonstrated that the positional arrangement of the sNP mutations had no effect on PsA-total or free-values (H (10) = 10.92, p = 0.28;H (10) = 10.07, p = 0.38 respectively). Two sNPs: rs6072 and rs74478031 were associated with elevated PsA levels (p sence, therefore, has the potential to serve, in conjunction with raised PsA, as biomarkers of prostate cancer in the study population.

关键词： Prostate Cancer Prostate-specific Antigen Kallikrein 2 Gene Genetic Mutations Haplotypes short Nucleotidepolymorphism

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