Evaluation of the Copy Number Variants and Single-Nucleotide Polymorphisms of ABCA3 in Newborns with Respiratory Distress Syndrome-A Pilot Study.

Background and Objectives: Respiratory distress syndrome (RDS) in preterm infants commonly occurs due to the immaturity-related deficiency of pulmonary surfactant. Beyond prematurity, various environmental and genetic factors can influence the onset and progression of RDS. This study aimed to analyze three single-nucleotide polymorphisms (SNPs) of the ABCA3 gene to assess the ABCA3 gene as a candidate gene for susceptibility to RDS and overall survival in newborns and to evaluate the utility of MLPA in RDS neonatal patients. Materials and Methods: Three SNPs were chosen and genotyped in a cohort of 304 newborns. Data analysis and statistical tests were employed to examine allele frequencies, haplotypes, and measures of pairwise linkage disequilibrium. Results: There was no observed haplotype association with SNPs rs13332514 (c.1059G>A) and rs170447 (c.1741+33T>C) among newborns, both with and without RDS (p > 0.05). The minor C allele frequency of the ABCA3 rs323043 (c.1755G>C) SNP showed a significant increase in preterm infants with RDS. MLPA results indicated that the predominant findings were normal, revealing no CNVs in the genes ABCA3 and SFTPC that were investigated in our patients. Conclusions: The presence of the variant C allele in the rs323043 (c.1755G>C) SNP may be a risk factor for RDS in premature newborns.

The Role of DNA Repair (XPC, XPD, XPF, and XPG) Gene Polymorphisms in the Development of Myeloproliferative Neoplasms.

Background and Objectives: Several polymorphisms have been described in various DNA repair genes. Nucleotide excision DNA repair (NER) detects defects of DNA molecules and corrects them to restore genome integrity. We hypothesized that the XPC, XPD, XPF, and XPG gene polymorphisms influence the appearance of myeloproliferative neoplasms (MPNs). Materials and Methods: We investigated the XPC 1496C>T (rs2228000, XPC Ala499Val), XPC 2920A>C (rs228001, XPC Lys939Gln), XPD 2251A>C (rs13181, XPD Lys751Gln), XPF-673C>T (rs3136038), XPF 11985A>G (rs254942), and XPG 3507G>C (rs17655, XPG Asp1104His) polymorphisms by polymerase chain reaction-restriction fragment length polymorphism analysis in 393 MPN patients [153 with polycythemia vera (PV), 201 with essential thrombocythemia (ET), and 39 with primary myelofibrosis (PMF)] and 323 healthy controls. Results: Overall, we found that variant genotypes of XPD 2251A>C were associated with an increased risk of MPN (OR = 1.54, 95% CI = 1.15-2.08, p = 0.004), while XPF-673C>T and XPF 11985A>G were associated with a decreased risk of developing MPN (OR = 0.56, 95% CI = 0.42-0.76, p < 0.001; and OR = 0.26, 95% CI = 0.19-0.37, p < 0.001, respectively). Conclusions: In light of our findings, XPD 2251A>C polymorphism was associated with the risk of developing MPN and XPF-673C>T and XPF 11985A>G single nucleotide polymorphisms (SNPs) may have a protective role for MPN, while XPC 1496C>T, XPC 2920A>C, and XPG 3507G>C polymorphisms do not represent risk factors in MPN development.

Analysis of Mutational Status of IGHV, and Cytokine Polymorphisms as Prognostic Factors in Chronic Lymphocytic Leukemia: The Romanian Experience.

The aim of the current study was to assess the associations between genetic risk factors (such as the mutational status of the IGHV gene and polymorphisms of the IL-10 and TNF-α genes) and CLL risk, prognosis, and overall survival. Another goal of this study was to evaluate the multivariate effect of the combination of multiple genetic risk factors (mutational status of the IGHV gene, somatic mutations, DNA CNVs, and cytokine SNPs) on the clinical characteristics and survival of patients. A total of 125 CLL patients and 239 healthy controls were included for comparative SNP analysis. IL-10 (rs1800896 and rs1800872) and TNF-α (rs361525 and rs1800750) SNPs and haplotypes were not associated with CLL risk. The absence of hypermutation in the IGHV gene was shown to be of important prognostic value, being associated with short OS. Further individual risk factors for short OS were an age above 65 years at diagnosis and the presence of somatic mutations and/or CNVs. In our multivariable analysis, the presence of somatic mutations and the IL-10 rs1800872 variant allele, and the association of CNVs with the IL-10 rs1800896 variant allele, were identified as risk factors for short OS. Moreover, the OS in unmutated IGHV patients was additionally affected (decreased) by the presence of CNVs and/or somatic mutations. Similarly, IL-10 rs1800896 modulated the OS in unmutated IGHV patients with CNVs.

Descriptive and Functional Genomics in Neonatal Respiratory Distress Syndrome: From Lung Development to Targeted Therapies.

In this up-to-date study, we first aimed to highlight the genetic and non-genetic factors associated with respiratory distress syndrome (RDS) while also focusing on the genomic aspect of this condition. Secondly, we discuss the treatment options and the progressing therapies based on RNAs or gene therapy. To fulfill this, our study commences with lung organogenesis, a highly orchestrated procedure guided by an intricate network of conserved signaling pathways that ultimately oversee the processes of patterning, growth, and differentiation. Then, our review focuses on the molecular mechanisms contributing to both normal and abnormal lung growth and development and underscores the connections between genetic and non-genetic factors linked to neonatal RDS, with a particular emphasis on the genomic aspects of this condition and their implications for treatment choices and the advancing therapeutic approaches centered around RNAs or gene therapy.