Two Novel Polymorphisms in 5' Flanking Region of the Mesothelin Gene are Associated with Soluble Mesothelin-Related Peptide (SMRP) Levels

2011 ◽  
Vol 26 (2) ◽  
pp. 117-123 ◽  
Author(s):  
Alfonso Cristaudo ◽  
Rudy Foddis ◽  
Alessandra Bonotti ◽  
Silvia Simonini ◽  
Agnese Vivaldi ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Fold Increase ◽  
High Rate ◽  
Pleural Mesothelioma ◽  
Clinical Use ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Elisa Kit ◽  
Surveillance Programs ◽  
Flanking Region

Background and aims Increased concentrations of soluble mesothelin-related peptides (SMRP) have been found in sera of patients with malignant pleural mesothelioma (MPM) even if a relatively high rate of false positives has hampered their clinical use as a tumor marker. Individual SMRP levels could be affected by polymorphic elements. The aim of this study was to investigate the association between single nucleotide polymorphisms within the promoter-5'UTR regions and SMRP levels in healthy asbestos-exposed individuals and patients suffering from MPM. Methods The promoter-5'UTR regions of the mesothelin gene were genotyped in 59 healthy asbestos-exposed subjects and 27 MPM patients. SMRP levels were measured using a commercially available ELISA kit. Results Two novel polymorphisms, an A>C variant (called New1) and a C>T variant (called New2), were identified. In healthy subjects, high SMRP levels were associated with the C-variant of New1, with an average 1.62-fold increase compared with AA homozygotes (p<0.0001). Most of the C-allele carriers had SMRP levels above the threshold of 1.00 nM. We set two different SMRP cutoffs on the basis of the combined New1+New2 genotypes. Conclusions New1-New2 genotypes could be employed as markers for setting individualized and appropriate thresholds of “normality” when SMRP is used in surveillance programs of asbestos-exposed people.

scholarly journals Serotype Is Associated With High Rate of Colistin Resistance Among Clinical Isolates of Salmonella

2020 ◽  
Vol 11 ◽  
Author(s):  
Qixia Luo ◽  
Yuan Wang ◽  
Hao Fu ◽  
Xiao Yu ◽  
Beiwen Zheng ◽  
...  
Keyword(s):  
Clinical Microbiology ◽  
Core Genome ◽  
Clinical Isolates ◽  
High Rate ◽  
Clinical Microbiology Laboratory ◽  
Nucleotide Polymorphisms ◽  
Microbiology Laboratory ◽  
Colistin Resistance ◽  
Single Nucleotide ◽  
Blood Samples

To investigate the prevalence, probable mechanisms and serotype correlation of colistin resistance in clinical isolates of Salmonella from patients in China, Salmonella isolates were collected from fecal and blood samples of patients. In this study, 42.8% (136/318) clinical isolated Salmonella were resistant to colistin. MIC distribution for colistin at serotype level among the two most prevalent serotypes originating from humans in China indicated that Salmonella Enteritidis (83.9% resistance, 125/149) were significantly less susceptible than Salmonella Typhimurium (15.3% resistance, 9/59, P &lt; 0.01). mcr genes and mutations in PmrAB confer little for rate of colistin resistant Salmonella isolated from human patients. Phylogenetic tree based on core-genome single nucleotide polymorphisms (SNPs) was separately by the serotypes and implied a diffused distribution of MICs in the same serotype isolates. Relatvie expression levels of colistin resistant related pmr genes were significantly higher in non-mcr colistin resistant S. Typhimurium than in colistin sensitive S. Typhimurium, but no discernable differences between colistin resistant and sensitive S. Enteritidis, indicating a different mechanism between colistin resistant S. Typhimurium and S. Enteritidis. In conclusion, colistin susceptibility and colistin resistant mechanism of clinical isolated Salmonella were closely associated with specific serotypes, at least in the two most prevalent serotype Enteritidis and Typhimurium. We suggest clinical microbiology laboratory interpreting Salmonella colistin MIC results in the serotype level.

scholarly journals FUT2, Secretor Status and FUT3 Polymorphisms of Children with Acute Diarrhea Infected with Rotavirus and Norovirus in Brazil

Viruses ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 1084
Author(s):  
Marco André Loureiro Tonini ◽  
Débora Maria Pires Gonçalves Barreira ◽  
Luciana Bueno de Freitas Santolin ◽  
Lays Paula Bondi Volpini ◽  
José Paulo Gagliardi Leite ◽  
...  
Keyword(s):  
Acute Diarrhea ◽  
Current Knowledge ◽  
Host Susceptibility ◽  
High Rate ◽  
Southeastern Brazil ◽  
Blood Group Antigens ◽  
Nucleotide Polymorphisms ◽  
Symptomatic Infection ◽  
Single Nucleotide ◽  
Secretor Status

Host susceptibility according to human histo-blood group antigens (HBGAs) is widely known for norovirus infection, but is less described for rotavirus. Due to the variable HBGA polymorphism among populations, we aimed to evaluate the association between HBGA phenotypes (ABH, Lewis and secretor status) and susceptibility to rotavirus and norovirus symptomatic infection, and the polymorphisms of FUT2 and FUT3, of children from southeastern Brazil. Paired fecal-buccal specimens from 272 children with acute diarrhea were used to determine rotavirus/norovirus genotypes and HBGAs phenotypes/genotypes, respectively. Altogether, 100 (36.8%) children were infected with rotavirus and norovirus. The rotavirus P[8] genotype predominates (85.7%). Most of the noroviruses (93.8%) belonged to genogroup II (GII). GII.4 Sydney represented 76% (35/46) amongst five other genotypes. Rotavirus and noroviruses infected predominantly children with secretor status (97% and 98.5%, respectively). However, fewer rotavirus-infected children were Lewis-negative (8.6%) than the norovirus-infected ones (18.5%). FUT3 single nucleotide polymorphisms (SNP) occurred mostly at the T59G > G508A > T202C > C314T positions. Our results reinforce the current knowledge that secretors are more susceptible to infection by both rotavirus and norovirus than non-secretors. The high rate for Lewis negative (17.1%) and the combination of SNPs, beyond the secretor status, may reflect the highly mixed population in Brazil.

scholarly journals Mineral Nutrition and the Risk of Chronic Diseases: A Mendelian Randomization Study

Nutrients ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 378 ◽  
Author(s):  
Wen-Wen Cheng ◽  
Qiang Zhu ◽  
Hong-Yu Zhang
Keyword(s):  
Chronic Diseases ◽  
Mendelian Randomization ◽  
Fold Increase ◽  
Nucleotide Polymorphisms ◽  
Major Depressive ◽  
Standard Deviation Increase ◽  
Single Nucleotide ◽  
Unit Increase ◽  
Calcium Magnesium

We applied Mendelian randomization analyses to investigate the potential causality between blood minerals (calcium, magnesium, iron, copper, and zinc) and osteoporosis (OP), gout, rheumatoid arthritis (RA), type 2 diabetes (T2D), Alzheimer's disease (AD), bipolar disorder (BD), schizophrenia , Parkinson’s disease and major depressive disorder. Single nucleotide polymorphisms (SNPs) that are independent (r2 < 0.01) and are strongly related to minerals (p < 5 × 10−8) are selected as instrumental variables. Each standard deviation increase in magnesium (0.16 mmol/L) is associated with an 8.94-fold increase in the risk of RA (p = 0.044) and an 8.78-fold increase in BD (p = 0.040) but a 0.10 g/cm2 increase in bone density related to OP (p = 0.014). Each per-unit increase in copper is associated with a 0.87-fold increase in the risk of AD (p = 0.050) and BD (p = 0.010). In addition, there is suggestive evidence that calcium is positively correlated (OR = 1.36, p = 0.030) and iron is negatively correlated with T2D risk (OR = 0.89, p = 0.010); both magnesium (OR = 0.26, p = 0.013) and iron (OR = 0.71, p = 0.047) are negatively correlated with gout risk. In the sensitivity analysis, causal estimation is not affected by pleiotropy. This study supports the long-standing hypothesis that magnesium supplementation can increase RA and BD risks and decrease OP risk and that copper intake can reduce AD and BD risks. This study will be helpful to address some controversial debates on the relationships between minerals and chronic diseases.

Single nucleotide polymorphisms (SNPs) analysis of CYP2C8, GSTT1, GSTP1, MDR1(A), MDR1(B) and ERCC1 as predictor of survival after weekly paclitaxel for relapsed advanced head & neck cancer patients (AHNCP)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 2540-2540 ◽  
Author(s):  
J. J. Grau ◽  
M. Monzo ◽  
M. Vargas ◽  
S. Jansa ◽  
m. Campayo ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Phase 1 ◽  
High Rate ◽  
Weekly Paclitaxel ◽  
Head Neck Cancer ◽  
Nucleotide Polymorphisms ◽  
Wild Type ◽  
Single Nucleotide ◽  
The Status ◽  
Head Neck

2540 Background: Gene SNPs correlate with survival in cancer patients (pts) treated with chemotherapy (CHM). CYP2C8 and GSTT1, GTSP1 genes are involved in phase 1 and 2 drug cellular metabolisms respectively; MDR1(A) and MDR1(B) are involved in drug membrane transport and ERCC1 in DNA repair Methods: We evaluated the presence of SNPs of these 6 genes and the survival of AHNCP treated with weekly paclitaxel, 80 mg/m2 iv for 6 weeks. Responding pts continue CHM till progression. All pts were cisplatin resistant and no other local therapies were available. We analysed paraffin-embedded biopsies from 47 consecutive AHNCP for SNPs of the mentioned genes. The status of the alleles wild type (wt) or at least 1 SNP was compared with response rate (RR), time to progression (TTP) and overall survival (OS) Results: Of 47 pts, 43 were male and 4 female. The median of age was 57 yr (46–80). RR was 45% (21/47) and the TTP in responders was 5 months of median. OS for all pts was 5.6 months. Wild type vs at least 1 SNPs frequencies according the genes were: CYP2C8 23/24; GSTT1 45/2; GSTP1 36/11; MDR1(A) 21/28; MDR1(B) 13/34; and ERCC1 27/20. OS was significantly better in pts with 2 or more SNPs accumulated (p=0.0455). No other significant differences were observed in RR, TTP or OS in SNPs vs wild type pts. Conclusions: SNPs of CYP2C8, MDR1(A) and MDR1(B) genes were more frequent than wt in our pts. OS was significantly better in pts with 2 or more SNPs accumulated. Paclitaxel provides high rate of responses of short duration in AHNC pts No significant financial relationships to disclose.

scholarly journals Loss of Imprinting of IGF2 Gene in the Chorionic Tissues of Spontaneously Eliminated Human Embryos

2013 ◽  
Vol 5 ◽  
pp. GEG.S11460 ◽  
Author(s):  
Danuta Zastavna ◽  
Halyna Makukh ◽  
Bogdan Tretjak ◽  
Olena Bilevych ◽  
Miroslaw Tyrka
Keyword(s):  
Genomic Imprinting ◽  
Gene Locus ◽  
Fold Increase ◽  
Cell Types ◽  
Prenatal Development ◽  
Human Embryos ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Igf2 Gene ◽  
Loss Of Imprinting

Insulin-like growth factor-2 (IGF-2) is a mitogen, growth and differentiation modulator for many cell types. It is mainly expressed during the prenatal development, and its activity strongly depends on the genomic imprinting. Genomic imprinting in the chorionic tissues of spontaneously eliminated human embryos has been studied on the model of 820-AG (Apa1) of the IGF-2 gene locus. Molecular and genetic analysis was performed on the polymorphic 820-AG IGF2 locus in 107 samples of DNA extracted from the chorionic tissues of spontaneously eliminated human embryos within 5–10 weeks of gestation. Presence of AG genotype Apa 1 single nucleotide polymorphisms of the IGF-2 was shown to cause more than a 7-fold increase in the risk of embryo elimination. Thus, the loss of genomic imprinting of the IGF-2 gene may be an important cause of the miscarriages in human.

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