scholarly journals Association of ACE2 Polymorphisms and Derived Haplotypes with Obesity and Hyperlipidemia in Female Spanish Adolescents

2021 ◽  
Author(s):  
J. Lumpuy-Castillo ◽  
C. Vales-Villamarín ◽  
I. Mahíllo-Fernández ◽  
I. Pérez-Nadador ◽  
L. Soriano-Guillén ◽  
...  
Keyword(s):  
Plasma Lipids ◽  
Molecular Targets ◽  
Predictive Biomarkers ◽  
Overweight And Obesity ◽  
Ang Ii ◽  
Nucleotide Polymorphisms ◽  
Plasma Parameters ◽  
Single Nucleotide ◽  
High Degree ◽  
Stimulation Of

Abstract Background In the cardiovascular (CV) system, overactivation of the angiotensin converting enzyme (ACE) may trigger deleterious responses derived from angiotensin (Ang)-II, which can be attenuated by stimulation of ACE2 and subsequent Ang-(1-7) metabolite. However, ACE2 exhibits a high degree of genetic polymorphism that may affect its structure and stability, interfering with these cardioprotective actions. Methodology: Five ACE2-single nucleotide polymorphisms (SNP); rs4646188, rs2158083, rs233575, rs879922, and rs2074192, previously related with CV risk factors, were analyzed in a general population of adolescents and tested for potential associations with anthropometric and plasma parameters. Results Girls (n=461) exhibited lower rates of overweight and obesity, blood pressure, and glycemia than boys (n=412), though increased plasma lipids. The triglycerides (TG)/HDL-C ratio was, however, lower in females. Interestingly, only in girls, the occurrence of overweight/obesity was associated with the SNPs rs879922 [OR 1.67 (1.02-2.75)], rs233575 [OR 1.98 (1.21- 3.22)] and rs2158083 [OR 1.67 (1.04-2.68)]. Also, their highest levels of TG were linked to rs879922, rs233575, and rs2158083, and the highest TG/HDL-C ratio was assocated with rs879922 and rs233575. The upper levels of TC and LDL-C was associated with rs2074192 and rs2158083. Furthermore, the established cut-off level for TG ≥ 90 mg/dl was related with rs879922 [OR 1.78 (1.06-2.96)], rs2158083 [OR 1.75 (1.08-2.82)], and rs233575 [OR 1.62 (1.00 -2.61)]. The cut-off level for TC ≥ 170 mg/dl was associated with rs2074192 [OR 1.54 (1.04-2.28) and rs2158083 [OR 1.53 (1.04-2.25)]. In addition, the haplotype (C-G-C) derived from rs879922-rs2158083-rs233575 was related with higher prevalence of overweight/obesity and TG elevation. Conclusion The expression and activity of ACE2 may be essential for CV homeostasis. Interestingly, ACE2-SNPs rs879922, rs233575, rs2158083 and rs2074192, and haplotype (C-G-C) of the three former could induce vulnerability to obesity and hyperlipidemia in women. Thus, these SNPs might be used as predictive biomarkers for CV diseases and as molecular targets for CV therapy.

scholarly journals Association of ACE2 Polymorphisms and Derived Haplotypes With Obesity and Hyperlipidemia in Female Spanish Adolescents

2021 ◽  
Author(s):  
J. Lumpuy-Castillo ◽  
C. Vales-Villamarín ◽  
I. Mahíllo-Fernández ◽  
I. Pérez-Nadador ◽  
L. Soriano-Guillén ◽  
...  
Keyword(s):  
Plasma Lipids ◽  
Molecular Targets ◽  
Predictive Biomarkers ◽  
Overweight And Obesity ◽  
Ang Ii ◽  
Nucleotide Polymorphisms ◽  
Plasma Parameters ◽  
Single Nucleotide ◽  
High Degree ◽  
Stimulation Of

Abstract Background: In the cardiovascular (CV) system, overactivation of the angiotensin converting enzyme (ACE) may trigger deleterious responses derived from angiotensin (Ang)-II, which can be attenuated by stimulation of ACE2 and subsequent Ang-(1-7) metabolite. However, ACE2 exhibits a high degree of genetic polymorphism that may affect its structure and stability, interfering with these cardioprotective actions. Methodology: Five ACE2-single nucleotide polymorphisms (SNP); rs4646188, rs2158083, rs233575, rs879922, and rs2074192, previously related with CV risk factors, were analyzed in a general population of adolescents and tested for potential associations with anthropometric and plasma parameters.Results: Girls (n=461) exhibited lower rates of overweight and obesity, blood pressure, and glycemia than boys (n=412), though increased plasma lipids. The triglycerides (TG)/HDL-C ratio was, however, lower in females. Interestingly, only in girls, the occurrence of overweight/obesity was associated with the SNPs rs879922 [OR 1.67 (1.02-2.75)], rs233575 [OR 1.98 (1.21- 3.22)] and rs2158083 [OR 1.67 (1.04-2.68)]. Also, their highest levels of TG were linked to rs879922, rs233575, and rs2158083, and the highest TG/HDL-C ratio was assocated with rs879922 and rs233575. The upper levels of TC and LDL-C was associated with rs2074192 and rs2158083. Furthermore, the established cut-off level for TG ≥ 90 mg/dl was related with rs879922 [OR 1.78 (1.06-2.96)], rs2158083 [OR 1.75 (1.08-2.82)], and rs233575 [OR 1.62 (1.00 -2.61)]. The cut-off level for TC ≥ 170 mg/dl was associated with rs2074192 [OR 1.54 (1.04-2.28) and rs2158083 [OR 1.53 (1.04-2.25)]. In addition, the haplotype (C-G-C) derived from rs879922-rs2158083-rs233575 was related with higher prevalence of overweight/obesity and TG elevation. Conclusion: The expression and activity of ACE2 may be essential for CV homeostasis. Interestingly, ACE2-SNPs rs879922, rs233575, rs2158083 and rs2074192, and haplotype (C-G-C) of the three former could induce vulnerability to obesity and hyperlipidemia in women. Thus, these SNPs might be used as predictive biomarkers for CV diseases and as molecular targets for CV therapy.

scholarly journals High Degree of Single Nucleotide Polymorphisms in California Culex pipiens (Diptera: Culicidae) sensu lato

2012 ◽  
Vol 49 (2) ◽  
pp. 299-306 ◽  
Author(s):  
Yoosook Lee ◽  
Stephanie N. Seifert ◽  
Catelyn C. Nieman ◽  
Rory D. McAbee ◽  
Parker Goodell ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Culex Pipiens ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
High Degree

scholarly journals Limited genetic diversity of blaCMY-2-containing IncI1-pST12 plasmids from Enterobacteriaceae of human and broiler chicken origin in the Netherlands

2020 ◽  
Author(s):  
Evert den Drijver ◽  
Joep J.J.M. Stohr ◽  
Jaco J. Verweij ◽  
Carlo Verhulst ◽  
Francisca C. Velkers ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Sequence Data ◽  
Sequence Similarity ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Pan Genome ◽  
Long Read ◽  
Short Read Sequence ◽  
High Degree ◽  
Limited Genetic Diversity

AbstractDistinguishing epidemiologically related and unrelated plasmids is essential to confirm plasmid transmission. We compared IncI1-pST12 plasmids from both human and livestock origin and explored the degree of sequence similarity between plasmids from Enterobacteriaceae with different epidemiological links. Short-read sequence data of Enterobacteriaceae cultured from humans and broilers were screened for the presence of both a blaCMY-2 gene and an IncI1-pST12 replicon. Isolates were long-read sequenced on a MinION sequencer (OxfordNanopore Technologies). After plasmid reconstruction using hybrid assembly, pairwise single nucleotide polymorphisms (SNP) were determined. The plasmids were annotated, and a pan-genome was constructed to compare genes variably present between the different plasmids. Nine Escherichia coli sequences of broiler origin, four Escherichia coli sequences and one Salmonella enterica sequence of human origin were selected for the current analysis. A circular contig with the IncI1-pST12 replicon and blaCMY-2 gene was extracted from the assembly graph of all fourteen isolates. Analysis of the IncI1-pST12 plasmids revealed a low number of SNP differences (range of 0-9 SNPs). The range of SNP differences overlapped in isolates with different epidemiological links. One-hundred and twelve from a total of 113 genes of the pan-genome were present in all plasmid constructs. NGS-analysis of blaCMY--2-containing IncI1-pST12 plasmids isolated from Enterobacteriaceae with different epidemiological links show a high degree of sequence similarity in terms of SNP differences and the number of shared genes. Therefore, statements on the horizontal transfer of these plasmids based on genetic identity should be made with caution.

scholarly journals Single nucleotide polymorphisms as prognostic and predictive biomarkers in renal cell carcinoma

Oncotarget ◽  
2017 ◽  
Vol 8 (63) ◽  
pp. 106551-106564 ◽  
Author(s):  
Carmen Garrigós ◽  
Marta Espinosa ◽  
Ana Salinas ◽  
Ignacio Osman ◽  
Rafael Medina ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Single Nucleotide Polymorphisms ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Predictive Biomarkers ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide

Single-nucleotide polymorphisms (SNPs) associated with outcomes in patients with localized and metastatic renal cell carcinoma (RCC).

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 437-437
Author(s):  
Carmen Garrigos ◽  
Marta Espinosa ◽  
Ignacio Osman ◽  
Rainiero Ávila ◽  
Rafael Medina ◽  
...  
Keyword(s):  
Disease Free Survival ◽  
Predictive Biomarkers ◽  
Response To Treatment ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Free Survival ◽  
Snp Data ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Vegf Isoforms

437 Background: Despite major advances in the knowledge of the molecular basis of RCC, prognosis is still defined using clinical and pathological parameters. Moreover, no valid predictive biomarkers exist to help us selecting the best treatment for each patient. The aim of this work is analyzing the expression and determining the prognostic and predictive value of 64 key SNPs in 18 genes related with angiogenesis or metabolism of antiangiogenics in patients (pts) with both localized and advanced RCC treated at Hospital Universitario Virgen del Rocío. Methods: DNA from formalin fixed paraffin embedded tumor and non-tumor samples from 99 pts with RCC (26 advanced/ 73 localized) was extracted with QiAGEN Kit and amplified with a specific primers pool for every SNP as determined by the manufacturer (Lifetech). 64 SNPs were chosen based on their Minor Allele Frequency by HapMap, linkage disequilibrium by Haploview, and information from SNP data base (dSNP) and were studied by TaqMan OpenArray (Lifetech). The presence of the selected SNPs was correlated with clinical features, disease free survival (DFS), overall survival (OS), and response to treatment (RR). SPSS v16 was utilized for statistical analyses. Results: In pts with localized RCC, 6 SNPs in 3 genes involved in angiogenesis predicted for worse DFS (VEGFR2: rs10013228, rs2071559; PDGFRA: rs2228230) and shorter OS (VEGFR2: rs10013228; VEGFR3: rs6877011, rs307826) (p<0.05). In the advanced setting, 7 SNPs in genes related to both angiogenesis and metabolism of antiangiogenics determined inferior OS (IL8: rs2227543, NR1l2: rs3814055, NR1l3: rs2307424, PDGFA: rs9800958, PDGFRB: rs2302273) and worse RR (VEGFA: rs699947, rs3025010 p<0.01)). Additionally 3 SNPs in PDGFR-B and VEGF isoforms predicted for better RR (PDGFRB: rs17708574 (p=0.08), VEGFB: rs594942 (p=0.03), VEGFC: rs2016110 (p=0.07). Conclusions: Genetic analysis of RCC patients might provide valuable prognostic/predictive information. A set of SNPs in genes critical to angiogenesis and metabolism of antiangiogenics seem to determine post-surgical outcomes and treatment response in our series. These results are promising. Validation of the results is ongoing.

Novel and nondetected human signaling protein polymorphisms

2002 ◽  
Vol 10 (3) ◽  
pp. 159-168 ◽  
Author(s):  
Roy A. Lynch ◽  
Lynne Wagoner ◽  
Shunan Li ◽  
Li Sparks ◽  
Jeffery Molkentin ◽  
...  
Keyword(s):  
Genomic Dna ◽  
Evolutionary Conservation ◽  
Nonsynonymous Snps ◽  
Signaling Proteins ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Signaling Protein ◽  
Downstream Signaling ◽  
Small G Protein ◽  
High Degree

The frequency of single nucleotide polymorphisms (SNPs) in downstream signaling proteins was determined by combination heteroduplex HPLC and double-stranded sequencing of genomic DNA from 96–144 congestive heart failure (CHF) patients. Analysis of 56 coding exons in 9 signaling genes revealed 17 novel and 8 previously reported synonymous (no change in amino acid) SNPs, as well as one novel nonsynonymous SNP in the Rad small G protein. Because this initial analysis failed to detect numerous SNPs reported in the NCBI and Celera databases, double-strand sequencing of relevant exons from 74–91 CHF patients was used to confirm the absence of 10 previously reported nonsynonymous SNPs. Our results show that synonymous SNPs are frequent in signaling protein genes, whereas nonsynonymous SNPs are rare, suggesting a high degree of evolutionary conservation among these downstream signaling molecules. Comparisons of our results to the NCBI and Celera databases indicates that 56% of their SNP entries are not detected in our cohort. Importantly, while 31% of database SNPs were verified, 69% of SNPs detected in our cohort are not included in these databases. These findings indicate that caution may be warranted in relying exclusively on SNP databases as catalogs for polymorphic signaling protein genes.

scholarly journals ATXN7 Gene Variants and Expression Predict Post-Operative Clinical Outcomes in Hepatitis B Virus-Related Hepatocellular Carcinoma

2016 ◽  
Vol 39 (6) ◽  
pp. 2427-2438 ◽  
Author(s):  
Chuangye Han ◽  
Long Yu ◽  
Xiaoguang Liu ◽  
Tingdong Yu ◽  
Wei Qin ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Outcomes ◽  
Pcr Amplification ◽  
Predictive Biomarkers ◽  
Therapeutic Effects ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
B Virus ◽  
Serum Alpha Fetoprotein ◽  
High Level

Background/Aims: Hepatocellular carcinoma (HCC) is a lethal disease with nearly equal morbidity and mortality. Thus, the discovery and application of more useful predictive biomarkers for improving therapeutic effects and prediction of clinical outcomes is of crucial significance. Methods: A total of 475 HBV-related HCC patients were enrolled. Ataxin 7 (ATXN7) single nucleotide polymorphisms (SNPs) were genotyped by Sanger DNA sequencing after PCR amplification. The associations between ATXN7 SNPs and mRNA expression with the prognosis of HBV-related HCC were analyzed. Results: In all, rs3774729 was significantly associated with overall survival (OS) of HBV-related HCC (P = 0.013, HR = 0.66, 95% CI: 0.48-0.94). And patients with the AA genotype and a high level of serum alpha fetoprotein (AFP) had significantly worse OS when compared to patients with AG/GG genotypes and a low level of AFP (adjusted P = 0.007, adjusted HR = 1.83, 95% CI = 1.18-2.82). Furthermore, low expression of ATXN7 was significantly associated with poor recurrence-free survival (RFS) and OS (P = 0.007, HR = 2.38, 95% CI = 1.27-4.45 and P = 0.025, HR = 1.75, 95% CI = 1.18-2.62). Conclusion: ATXN7 may be a potential predictor of post-operative prognosis of HBV-related HCC.

Detection of the antimicrobial peptide gene in different Amaranthus species

Biologia ◽  
2008 ◽  
Vol 63 (2) ◽  
Author(s):  
Radka Pribylova ◽  
Petr Kralik ◽  
Bohumila Pisarikova ◽  
Ivo Pavlik
Keyword(s):  
Antimicrobial Peptide ◽  
Amino Acid Change ◽  
Sequence Similarity ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Amaranthus Caudatus ◽  
Amaranth Species ◽  
Pcr Products ◽  
Peptide Gene ◽  
High Degree

AbstractUsing primers to amplify the gene AMP2 in Amaranthus caudatus, we found the gene to be present in seven other species of the Amaranthus genus (A. albus, A. cruentus, A. blitum, A. hybridus, A. hypochondriacus, A. retroflexus and A. tricolor), in which it had not been described previously. The PCR products were sequenced and it was established that all the sequences were identical, except for two polymorphisms. These single nucleotide polymorphisms occurred at nucleotide positions 45 and 246. This exchange of one nucleotide for another was manifested in an amino acid change in both cases. Due to the fact that both polymorphisms lay outside the region encoding the chitin-binding peptide domain, which is crucial for antimicrobial peptide function, they will not likely affect the proper functioning of the peptide. With the exception of the above-mentioned polymorphisms, all sequences were identical to the sequence of the AMP2 gene that codes for the A. caudatus Ac-AMP2 (antimicrobial peptide isolated from Amaranthus caudatus seeds). The detection of sequences with high degree of sequence similarity to A. caudatus AMP2 gene leads us to the assumption that an antimicrobial peptide could also be produced by other amaranth species.

Hyperphosphorylation of autoantigenic targets of paraproteins is due to inactivation of PP2A

Blood ◽  
2011 ◽  
Vol 118 (12) ◽  
pp. 3340-3346 ◽  
Author(s):  
Klaus-Dieter Preuss ◽  
Michael Pfreundschuh ◽  
Natalie Fadle ◽  
Evi Regitz ◽  
Sybille Raudies ◽  
...  
Keyword(s):  
Genetic Defect ◽  
Catalytic Subunit ◽  
General Mechanism ◽  
Nucleotide Polymorphisms ◽  
Wild Type ◽  
Single Nucleotide ◽  
Binding Epitope ◽  
Phosphatase 2A ◽  
Healthy Carriers ◽  
Stimulation Of

Abstract Paratarg-7, a frequent autoantigenic target, and all other autoantigenic targets of human paraproteins molecularly defined to date are hyperphosphorylated in the respective patients compared with healthy controls, suggesting that hyperphosphorylation of autoantigenic paraprotein targets is a general mechanism underlying the pathogenesis of these paraproteins. We now show that hyperphosphorylation of paratarg-7 occurs because of an additional phosphorylation of Ser17, which is located within the paraprotein-binding epitope. Coimmunoprecipitation identified phosphokinase C ζ (PKCζ) as the kinase responsible for the phosphorylation of most, and phosphatase 2A (PP2A) as the phosphatase responsible for the dephosphorylation of all hyperphosphorylated autoantigenic targets of paraproteins. Single-nucleotide polymorphisms (SNPs) or mutations of PKCζ and PP2A were excluded. However, PP2A was inactivated by phosphorylation of its catalytic subunit at Y307. Stimulation of T cells from healthy carriers of wild-type paratarg-7 induced a partial and transient hyperphosphorylation between days 4 and 18, which was maintained by incubation with inhibitors of PP2A, again indicating that an inactivation of PP2A is responsible for the hyperphosphorylation of autoantigenic paraprotein targets. We conclude that the genetic defect underlying the dominantly inherited hyperphosphorylation of autoantigenic paraprotein targets is not in the PP2A itself, but in genes or proteins controlling PP2A activity by phosphorylation of its catalytic subunit.

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