Table_1_The antigen processing-associated transporter gene polymorphism: Role on gene and protein expression in HPV-infected pre-cancerous cervical lesion.docx

Human papillomavirus (HPV) is the major pathogen for cervical lesions. The evasion mechanism of the immune response and persistence of HPV infection can be influenced by polymorphisms (SNPs) in genes associated with transporter associated with antigen processing (TAP), which may change the peptide binding affinity or the TAP expression impacting the efficiency of peptide transport in the secretory pathway, and the presentation of peptides to cytotoxic T lymphocytes. This study aimed to evaluate the role of the TAP1 and TAP2 polymorphisms, TAP1, and TAP2 genes expressions, and protein levels in cervical cells presenting different degrees of pre-cancerous lesions in 296 immunocompetent women infected or not by HPV. TAP SNPs were genotyped by Sanger sequencing, and gene expression by real-time PCR. Aneuploidy was determined by DNA index using flow cytometry. TAP-1 and TAP-2 tissue expressions were evaluated by immunohistochemistry. The Asp697Gly SNP of TAP1 presented a risk for cellular aneuploidy (P=0.0244). HPV+ women had higher TAP-2 mRNA (P=0.0212) and protein (P<0.0001) levels. The TAP2D and TAP2E haplotypes were associated with the risk for aneuploidy and pre-cancerous lesions. In conclusion, nucleotide variability at the peptide binding region of peptide transporter genes, particularly of the TAP2 gene, may influence the HPV-peptide transportation from the cytosol to the endoplasmic reticulum, increasing the susceptibility to the development of high-grade cervical lesions.</p

Clinical data of children with sickle cell anemia attended in Hemope Foundation—Recife/Brazil.

<p>Clinical data of children with sickle cell anemia attended in Hemope Foundation—Recife/Brazil.</p

Serum galectin-3 levels associated with <i>LGALS3</i> +191 (A) and +292 (B) genotypes in children with SCA.

<p><i>LGALS3</i> +191: C = reference allele; A = variant allele; <i>LGALS3</i> +292: A = reference allele; C = variant allele; +191 genotypes: CC vs. CA: <i>p <</i>0.0001; CC vs. AA: <i>p <</i>0.0001; CC vs. AA+CA: <i>p</i> <0.0001. +292 genotypes: AA vs. AC: <i>p</i> = 0.1684; AA vs. CC: <i>p</i> = 0.0046; AA vs. CC+AC: <i>p</i> = 0.0136. Mann-Whitney tests.</p

Serum galectin-3 levels are associated with <i>LGALS3</i> +191 and +292 combined genotypes in children with SCA.

<p>Statistical analysis of <i>LGALS3</i> combined genotype related of galectin-3 levels (high, intermediate and low) in which the serum concentrations in ng/ml were compared using Kruskal-Wallis test. High vs. intermediate: <i>p =</i> 0.1687; high vs. low: <i>p =</i> 0.0002; high vs. intermediate+low: <i>p</i> = 0.0098.</p

<i>LGALS3</i> +191 and +292 with vaso-occlusive crisis and respiratory tract infection in children with sickle cell anemia attended in Hemope Foundation—Recife/Brazil.

<p><i>LGALS3</i> +191 and +292 with vaso-occlusive crisis and respiratory tract infection in children with sickle cell anemia attended in Hemope Foundation—Recife/Brazil.</p

<i>LGALS3</i> +191 and +292 diplotype of serum levels with vaso-occlusive crisis and respiratory tract infection in children with sickle cell anemia attended in Hemope Foundation—Recife/Brazil.

<p><i>LGALS3</i> +191 and +292 diplotype of serum levels with vaso-occlusive crisis and respiratory tract infection in children with sickle cell anemia attended in Hemope Foundation—Recife/Brazil.</p

Single Nucleotide Polymorphisms at +191 and +292 of Galectin-3 Gene (<i>LGALS3</i>) Related to Lower GAL-3 Serum Levels Are Associated with Frequent Respiratory Tract Infection and Vaso-Occlusive Crisis in Children with Sickle Cell Anemia

<div><p>Introduction</p><p>Patients with sickle cell anemia (SCA) may present chronic hemolytic anemia, vaso-occlusion and respiratory tract infection (RTI) episodes. Galectin-3 (GAL-3) is a multifunctional protein involved in inflammation, apoptosis, adhesion and resistance to reactive oxygen species. Studies point to a dual role for GAL-3 as both a circulation damage-associated molecular pattern and a cell membrane associated pattern recognition receptor.</p><p>Objective</p><p>To investigate associations between the SNPs of GAL-3 gene (<i>LGALS3</i>) and serum levels with RTI and vaso-occlusive crisis (VOC) in children with SCA.</p><p>Materials and Methods</p><p>SNPs +191 and +292 in <i>LGALS3</i> were studied using the TaqMan real-time PCR system; GAL-3 serum levels were measured by ELISA. The study included 79 children with SCA ranging from 2 to 12 years old.</p><p>Results</p><p>GAL-3 serum levels were associated with <i>LGALS3</i> +191 and +292 genotypes (<i>p</i> <0.0001; <i>p</i> = 0.0169, respectively). <i>LGALS3</i> +191, AA genotype was associated with low and CC with higher levels of GAL-3. For <i>LGALS3</i> +292, the CC genotype was associated with lower GAL-3 and AA with higher levels. Patients with Frequency of RTI (FRTI) ≥1 presented higher frequency of +191AA (<i>p</i> = 0.0263) and +292AC/CC genotypes (<i>p</i> = 0.0320). SNP +292 was associated with Frequency of VOC (FVOC) (<i>p</i> = 0.0347), whereas no association was shown with SNP +191 and FVOC. However, CA/AC and AA/CC genotypes with lower GAL-3 levels showed a higher frequency in patients with FRTI ≥1 (<i>p</i> = 0.0170; <i>p</i> = 0.0138, respectively). Also, patients with FVOC ≥1 presented association with CA/AC (<i>p</i> = 0.0228). <i>LGALS3</i> +191 and +292 combined genotypes related to low (<i>p</i> = 0.0263) and intermediate expression (<i>p</i> = 0.0245) were associated with FRTI ≥1. Lower GAL-3 serum levels were associated with FRTI ≥1 (<i>p</i> = 0.0426) and FVOC ≥1 (<i>p</i> = 0.0012).</p><p>Conclusion</p><p>Variation of GAL-3 serum levels related to SNPs at +191 and +292 may constitute a susceptibility factor for RTI and VOC frequency.</p></div

Serum galectin-3 levels associated with frequency of respiratory tract infection (FRTI) and vaso-occlusive crisis (FVOC) in children with SCA.

<p>FRTI ≥1 vs. FRTI <1: <i>p</i> = 0.0426. FVOC ≥1 vs. FVOC <1: <i>p</i> = 0.0012. Mann-Whitney tests.</p

<i>LGALS3</i> +191 and +292 combined genotype distribution with vaso-occlusive crisis and respiratory tract infection in children with sickle cell anemia attended in Hemope Foundation—Recife/Brazil.

<p><i>LGALS3</i> +191 and +292 combined genotype distribution with vaso-occlusive crisis and respiratory tract infection in children with sickle cell anemia attended in Hemope Foundation—Recife/Brazil.</p