The aim of the present study was to investigate the influence of the nitric oxide synthase 3 (NOS3) 894 G>T polymorphism on prognostic outcomes of anthracycline in Chinese patients with de novo intermediate-risk acute myeloid leukaemia (AML) and to examine the gene expression level in relation to genetic variation. In all, 225 Chinese patients with intermediate-risk AML (at the complete remission stage) treated with anthracycline were enrolled in the study. The 894 G>T polymorphism of the NOS3 gene was analysed by allele-specific matrix-assisted laser desorption ionization time-of-flight. Expression of NOS3 mRNA was tested in 72 patients of known genotype for NOS3 894 G>T. The clinical characteristics of these patients were obtained from medical records. Survival analysis showed that patients with AML (GG genotype) had a longer overall survival (OS; P = 0.006). After adjusting for age, gender, leucocyte count, haemoglobin level, platelet level, French, American and Britain (FAB) classification, lactate dehydrogenase levels, Eastern Cooperative Oncology Group Performance Status, nucleophosmin gene and fms-related tyrosine kinase 3 gene, multivariate survival analysis showed that the NOS3 894 G>T polymorphism appeared to be a predicting factor for OS (P = 0.014; hazard ratio = 1.856). However, no significant associations between the NOS3 894 G>T polymorphism and relapse-free survival and relapse in patients with AML were observed. Gene expression levels were significantly higher in patients with the GG genotype than in patients with the GT and TT genotypes (P = 0.033). The findings suggest that the NOS3 894 G>T variant may be a biomarker for the prediction of OS in Chinese patients with AML.
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http://dx.doi.org/10.1111/1440-1681.12235 | DOI Listing |
Nat Commun
January 2025
Department of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter, Exeter, UK.
Investigating the genetic factors influencing human birth weight may lead to biological insights into fetal growth and long-term health. We report analyses of rare variants that impact birth weight when carried by either fetus or mother, using whole exome sequencing data in up to 234,675 participants. Rare protein-truncating and deleterious missense variants are collapsed to perform gene burden tests.
View Article and Find Full Text PDFBioelectrochemistry
February 2025
Department of Chemistry and Biochemistry, Ohio University, Athens, OH, USA. Electronic address:
The impact of four clinically significant genetic variants of endothelial nitric oxide synthase (eNOS) polymorphisms on the concentrations of nitric oxide [NO] and peroxynitrite [ONOO] has been given scant consideration. This study utilized a [NO]/[ONOO] ratio to determine the extent of endothelial dysfunction caused by these variations in the eNOS gene. The single nucleotide polymorphisms (T-786C, C-665T, and Glu298Asp) and a variable number of tandem repeats (intron 4 a/b/c) were genotyped in human umbilical vein endothelial cells (HUVEC), using sanger sequencing and DNA electrophoresis, respectively.
View Article and Find Full Text PDFmedRxiv
April 2024
Department of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter, Exeter, UK.
Investigating the genetic factors influencing human birth weight may lead to biological insights into fetal growth and long-term health. Genome-wide association studies of birth weight have highlighted associated variants in more than 200 regions of the genome, but the causal genes are mostly unknown. Rare genetic variants with robust evidence of association are more likely to point to causal genes, but to date, only a few rare variants are known to influence birth weight.
View Article and Find Full Text PDFBiochem Genet
December 2024
Department of Medical Laboratory Sciences-IUG, Gaza, Palestine.
Semen possesses a variety of antioxidant defense mechanisms which protect sperm DNA from the damaging effects of oxidative stress. Correlation between antioxidant genes variants and sperm DNA fragmentation (SDF) level is not sufficiently studied. Therefore, we investigated the association between several single nucleotide polymorphisms (SNPs): CYP1A1 (rs1048943A > G), CYP4F2 (rs2108622G > A), NRF2 (rs6721961C > A), PON1 (rs662A > G), NOS3 (rs1799983G > T), GSTM1 (null), CAT (rs1001179C > T), SOD2 (rs4880A > G), GSTP1 (rs1695A > G), PON2 (rs7493G > C), EPHX2 (rs1042064T > C), and AHR (rs2066853G > A) and elevated SDF.
View Article and Find Full Text PDFNature
November 2022
Bordeaux Population Health Research Center, University of Bordeaux, Inserm, UMR 1219, Bordeaux, France.
Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.
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