scholarly journals Examining the distribution and impact of single nucleotide polymorphisms in the capsular locus of Streptococcus pneumoniae serotype 19A

2021 ◽  
Author(s):  
D.W. Arends ◽  
W.R. Miellet ◽  
J.D. Langereis ◽  
T.H.A. Ederveen ◽  
C.E. van der Gaast - de Jongh ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Single Nucleotide Polymorphisms ◽  
Nucleotide Polymorphisms ◽  
Nucleotide Sugar ◽  
Single Nucleotide ◽  
Multiple Alleles ◽  
Enzymatic Function ◽  
Significant Difference ◽  
Sugar Levels ◽  
The Impact

Streptococcus pneumoniae serotype 19A prevalence has increased after implementation of PCV7 and PCV10 vaccines. In this study, we have provided, with high accuracy, the genetic diversity of the 19A serotype in a cohort of Dutch invasive pneumococcal disease patients and asymptomatic carriers obtained in the period 2004-2016. Whole genomes of the 338 pneumococcal isolates in this cohort were sequenced and their capsule ( cps ) loci compared to examine the diversity and determine the impact on the production of CPS sugar precursors and CPS shedding. We discovered 79 types with a unique CPS locus sequence. Most variation was observed in the rmlB and rmlD genes of the TDP-Rha synthesis pathway, and in the wzg gene, of unknown function. Interestingly, gene variation in the cps locus was conserved in multiple alleles. Using RmlB and RmlD protein models, we predict that enzymatic function is not affected by the single nucleotide polymorphisms as identified. To determine if RmlB and RmlD function was affected, we analyzed nucleotide sugar levels using UHPLC-MS. CPS precursors differed between 19A cps locus subtypes, including TDP-Rha, but no clear correlation was observed. Also, a significant difference in multiple nucleotide sugar levels was observed between phylogenetically branched groups. Because of indications of a role for Wzg in capsule shedding, we analyzed if this was affected. No clear indication of a direct role in shedding was found. We thus describe genotypic variety in rmlB , rmlD and wzg in serotype 19A the Netherlands, for which we have not discovered an associated phenotype.

scholarly journals Sex Differences in Circadian Clock Genes and Myocardial Infarction Susceptibility

2021 ◽  
Vol 8 (5) ◽  
pp. 53
Author(s):  
Ivana Škrlec ◽  
Jasminka Talapko ◽  
Martina Juzbašić ◽  
Robert Steiner
Keyword(s):  
Myocardial Infarction ◽  
Cardiovascular Disease ◽  
Circadian Rhythm ◽  
Single Nucleotide Polymorphisms ◽  
Clock Genes ◽  
P Value ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Biological Sex ◽  
Significant Difference

The growing body of evidence shows a significant difference in the circadian rhythm of cardiovascular disease based on biological sex. The incidence of cardiovascular disease varies between women and men. Additionally, biological sex is vital for the timely application of therapy—chronotherapy, which benefits both sexes. This study aimed to examine the potential difference of single nucleotide polymorphisms (SNPs) of the circadian rhythm genes ARNTL, CLOCK, CRY2 and PER2 in women and men with myocardial infarction. A cross-sectional study was conducted, including 200 patients with myocardial infarction. Altogether, ten single nucleotide polymorphisms in the ARNTL, CLOCK, CRY2 and PER2 genes were analyzed. The Chi-square test yielded statistically significant differences in CLOCK gene rs11932595 polymorphism in a recessive genotype model between women and men with a p-value of 0.03 and an odds ratio 2.66, and a corresponding 95% confidence interval of 1.07 to 6.66. Other analyzed polymorphisms of the circadian rhythm genes ARNTL, CRY2, and PER2 did not significantly differ between the sexes. According to the study’s current results, the CLOCK gene’s genetic variability might affect myocardial infarction concerning biological sex.

scholarly journals Nonsynonymous single nucleotide polymorphisms of NHE3 differentially decrease NHE3 transporter activity

2015 ◽  
Vol 308 (9) ◽  
pp. C758-C766 ◽  
Author(s):  
Xinjun Cindy Zhu ◽  
Rafiquel Sarker ◽  
John R. Horton ◽  
Molee Chakraborty ◽  
Tian-E Chen ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Large Fraction ◽  
Regulatory Protein ◽  
Nucleotide Polymorphisms ◽  
Genetic Determinants ◽  
Single Nucleotide ◽  
Mutant Proteins ◽  
Homologous Protein ◽  
Genetic Abnormalities ◽  
The Impact

Genetic determinants appear to play a role in susceptibility to chronic diarrhea, but the genetic abnormalities involved have only been identified in a few conditions. The Na+/H+ exchanger 3 (NHE3) accounts for a large fraction of physiologic intestinal Na+ absorption. It is highly regulated through effects on its intracellular COOH-terminal regulatory domain. The impact of genetic variation in the NHE3 gene, such as single nucleotide polymorphisms (SNPs), on transporter activity remains unexplored. From a total of 458 SNPs identified in the entire NHE3 gene, we identified three nonsynonymous mutations (R474Q, V567M, and R799C), which were all in the protein's intracellular COOH-terminal domain. Here we evaluated whether these SNPs affect NHE3 activity by expressing them in a mammalian cell line that is null for all plasma membrane NHEs. These variants significantly reduced basal NHE3 transporter activity through a reduction in intrinsic NHE3 function in variant R474Q, abnormal trafficking in variant V567M, or defects in both intrinsic NHE3 function and trafficking in variant R799C. In addition, variants NHE3 R474Q and R799C failed to respond to acute dexamethasone stimulation, suggesting cells with these mutant proteins might be defective in NHE3 function during postprandial stimulation and perhaps under stressful conditions. Finally, variant R474Q was shown to exhibit an aberrant interaction with calcineurin B homologous protein (CHP), an NHE3 regulatory protein required for basal NHE3 activity. Taken together, these results demonstrate decreased transport activity in three SNPs of NHE3 and provide mechanistic insight into how these SNPs impact NHE3 function.

scholarly journals The Impact of Single Nucleotide Polymorphisms on Human Aldehyde Oxidase

2012 ◽  
Vol 40 (5) ◽  
pp. 856-864 ◽  
Author(s):  
Tobias Hartmann ◽  
Mineko Terao ◽  
Enrico Garattini ◽  
Christian Teutloff ◽  
Joshua F. Alfaro ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Aldehyde Oxidase ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
The Impact

Genoset for CALCA and RAMP1 Single Nucleotide Polymorphisms Are Related to the Magnitude of Headache Symptoms After Concussion: A Preliminary Observation

Neurology ◽  
2021 ◽  
Vol 98 (1 Supplement 1) ◽  
pp. S22.3-S23
Author(s):  
Michael F. La Fountaine ◽  
Anthony Testa
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Saliva Sample ◽  
Area Under The Curve ◽  
Nucleotide Polymorphisms ◽  
Blurred Vision ◽  
Single Nucleotide ◽  
Commercial Laboratory ◽  
Pain Transmission ◽  
Significant Difference ◽  
A Prospective Study

ObjectiveDetermine whether single nucleotide polymorphisms (SNPs) of the calcitonin gene-related polypeptide (CGRP)-alpha (CALCA) and the receptor activity modifying protein-1 (RAMP1) are related to headache burden during the first week after concussion.BackgroundPost-traumatic headache is a commonly reported symptom after concussion. SNPs related to CGRP are involved in the pathogenesis of migraine headaches and contribute to pain transmission and neurogenic inflammation. It is unclear in concussed persons if the headache burden is associated with genetic variations related to CGRP.Design/MethodsA prospective study was performed in 34 concussed athletes (gender: 23 female, 11 male; age: 20 ± 1 years; height: 1.75 ± 0.12 meters; weight: 73 ± 14 kilograms). Participants completed the symptom evaluation checklist from the SCAT3 within 48 hours of injury (V1), and 4 (V2) and 7 (V3) days after injury. For each visit, the self-reported score (0–6) for headache, pressure in head, blurred vision, and sensitivity to light/noise were summed. The area under-the-curve (AUC) was computed for the early (EHB: V1 to V2) and late (LHB: V2 to V3) burden of headache-related symptoms. A saliva sample was obtained and a commercial laboratory identified the genotype for CALCA (rs3781719) and RAMP1 (rs10185142) using PMR-array. RAMP1 genotypes RAMP1 (TT, TC, CC) and CALCA (AA, AG, GG) genotypes were dichotomized (T+, T−, and A+, A− respectively) and concatenated (T + A+, T + A−, T−A+, T-A−) for analyses.ResultsA significant difference for EHB (p = 0.003, partial η2 = 0.417) was present across RAMP1+CALCA genotypes, but not for the LHB. The T + A+ subgroup had a significantly elevated EHB compared to the all-other subgroups (p < 0.05: T + A + [n = 16]: 31.6 ± 2.6; T + A − [n = 9]: 17.7 ± 3.6; T−A+ [n = 8]: 18.4 ± 3.7; T−A-[n = 1]: 0.0 ± 0.0). Gender served as a covariate and diagnosed concussion history had no impact.ConclusionsThe current analysis provides a proof-of-concept to suggest that the combined T + A+ genoset from RAMP1+CALCA are associated with a greater headache burden in the first 4 days after concussion injury.

scholarly journals ADIPOQ single nucleotide polymorphisms and breast cancer in northeastern Mexican women

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Ricardo M. Cerda-Flores ◽  
Karen Paola Camarillo-Cárdenas ◽  
Gabriela Gutiérrez-Orozco ◽  
Mónica Patricia Villarreal-Vela ◽  
Raquel Garza-Guajardo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Single Nucleotide Polymorphisms ◽  
Mexican Women ◽  
Genotype Distribution ◽  
Nucleotide Polymorphisms ◽  
Allelic Discrimination Assay ◽  
Allelic Discrimination ◽  
Single Nucleotide ◽  
Significant Difference ◽  
Hardy Weinberg Equilibrium

Abstract Background Adiponectin gene (ADIPOQ) polymorphisms have been shown to affect adiponectin serum concentration and some have been associated with breast cancer (BC) risk. The aims of this study were to describe the frequency of single nucleotide polymorphisms (SNPs) of ADIPOQ in Mexican women with BC and to determine if they show an association with it. Methods DNA samples from 397 patients and 355 controls were tested for the ADIPOQ gene SNPs: rs2241766 (GT) and rs1501299 (GT) by TaqMan allelic discrimination assay. Hardy–Weinberg equilibrium (HWE) was tested. Multiple SNP inheritance models adjusted by age and body mass index (BMI) were examined for the SNP rs1501299. Results We found that in the frequency analysis of rs1501299 without adjusting the BMI and age, the genotype distribution had a statistically significant difference (P = 0.003). The T allele was associated with a BC risk (OR, 1.99; 95% CI 1.13–3.51, TT vs. GG; OR, 1.53; 95% CI 1.12–2.09, GT vs. GG). The SNP rs2241766 was in HW disequilibrium in controls. In conclusion, the rs1501299 polymorphism is associated with a BC risk. Conclusions Identification of the genotype of these polymorphisms in patients with BC can contribute to integrate the risk profile in both patients and their relatives as part of a comprehensive approach and increasingly more personalized medicine.

The impact of single-nucleotide polymorphisms of human apurinic/apyrimidinic endonuclease 1 on specific DNA binding and catalysis

Biochimie ◽  
2019 ◽  
Vol 163 ◽  
pp. 73-83 ◽  
Author(s):  
Irina V. Alekseeva ◽  
Anastasiia T. Davletgildeeva ◽  
Olga V. Arkova ◽  
Nikita A. Kuznetsov ◽  
Olga S. Fedorova
Keyword(s):  
Dna Binding ◽  
Single Nucleotide Polymorphisms ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
The Impact
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