To our knowledge, this is the first article to examine the effect of a large number of genetics markers for phenotype prediction. The approach could be useful for forensic applications, as well as for the determination of possible phenotypes of extinct prehistoric individuals.
Human leukocyte antigen G (HLA-G) is an immunomodulatory molecule with important roles both physiologically as well as an escape mechanism of cancer cells. In this study, we evaluated the impact of eight polymorphisms at the 3' untranslated region (3'UTR) of the HLA-G gene in the development of prostate cancer (PCa) and benign prostatic hyperplasia (BPH). A total of 468 DNA samples of Brazilian men predominantly Euro-descendant with PCa (N = 187), BPH (N = 152) and healthy control individuals (N = 129) were evaluated. The HLA-G 3'UTR region was amplified by polymerase chain reaction (PCR), sequenced and genotyped to identify the 14 bp insertion/deletion (rs371194629), +3003T/C (rs1707), +3010C/G (rs1710), +3027A/C (rs17179101), +3035C/T (rs17179108), +3142G/C (rs1063320), +3187A/G (rs9380142) and +3196C/G (rs1610696) polymorphisms. Regression logistic and chi-square tests were performed to verify the influence of single nucleotide polymorphisms (SNPs) in PCa and/or BPH susceptibility, as well as in PCa progression (clinicopathological status). Our data showed the UTR-4 haplotype as a risk factor to PCa in comparison with control [odds ratio (OR) 2.35, 95% confidence interval (CI) 1.39-3.96, P adjusted = 0.003) and BPH groups (OR 1.82, 95% CI 1.15-2.86, P adjusted = 0.030). Further, the 'non-14bp Ins_ + 3142G_+3187A' haplotype (OR 1.56, 95% CI 1.10-2.20, P adjusted = 0.036), the +3003CT genotype (OR 4.44, 95% CI 1.33-4.50, P adjusted = 0.032) and the +3003C allele (OR 2.33, 95% CI 1.38-3.92, P adjusted = 0.016) also conferred susceptibility to PCa. Our data suggest an important influence of HLA-G 3'UTR polymorphisms in PCa susceptibility and support the use of the +3003 variant as a tag SNP for PCa risk.
MicroRNAs (miRNAs) are single-stranded sequences of non-coding RNA with approximately 22 nucleotides that act posttranscriptionally on gene expression. miRNAs are important gene regulators in physiological contexts, but they also impact the pathogenesis of various diseases. The role of miRNAs in viral infections has been explored by different authors in both population-based as well as in functional studies. However, the effect of miRNA polymorphisms on the susceptibility to viral infections and on the clinical course of these diseases is still an emerging topic. Thus, this review will compile and organize the findings described in studies that evaluated the effects of genetic variations on miRNA genes and on their binding sites, in the context of human viral diseases. In addition to discussing the basic aspects of miRNAs biology, we will cover the studies that investigated miRNA polymorphisms in infections caused by hepatitis B virus, hepatitis C virus, human immunodeficiency virus, Epstein–Barr virus, and human papillomavirus. Finally, emerging topics concerning the importance of miRNA genetic variants will be presented, focusing on the context of viral infectious diseases.
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