Prediction of prognosis in patients treated with everolimus for extrapancreatic neuroendocrine tumors by a single nucleotide polymorphism in PHLPP2.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 163-163 ◽  
Author(s):  
Seth Albert Bellister ◽  
Yunfei Zhou ◽  
Eric Sceusi ◽  
Lee M. Ellis ◽  
James C. Yao
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Neuroendocrine Tumors ◽  
Single Agent ◽  
Progression Free Survival ◽  
Wild Type ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Subset Analysis ◽  
Significant Difference

163 Background: Rapamycin analogs (rapalogs) have improved outcomes in patients with neuroendocrine tumors (NETs). Few factors affecting response to rapalogs have been characterized. PHLPP2 is a phosphatase that inhibits PI3K-Akt-mTOR signaling. We hypothesized that an inactivating single nucleotide polymorphism (SNP) in PHLPP2 may affect outcomes in NETs treated with the rapalog everolimus. Methods: Blood was collected from 32 patients enrolled in a Phase 2 single arm trial of single agent everolimus in patients with NETs. DNA was extracted and RT-PCR products were sequenced to detect the L1016S SNP in PHLPP2. Outcomes analyses determined the role of the SNP in predicting progression-free survival (PFS), overall survival (OS), and response rates (RR) in patients with NETs treated with everolimus. Response rate (RR) assessed by RECIST criteria was evaluated as a binomial endpoint. A subset analysis was conducted to evaluate the NET site-specific role of the SNP. Results: Overall median PFS was 15.2 months (95% Confidence Interval (CI)=11.5 -18.7). The PHLPP2 SNP did not predict for a significant difference in PFS (Median PFS; wild type vs. SNP 16.8 (95% CI=14-20) vs. 11.3 (95% CI=4-19) mos., respectively, Hazard Ratio (HR)=1.2 (95% CI=0.5-3.1)), p=0.154). In a subset analysis, patients with extra-pancreatic NETs treated with everolimus with wild type PHLPP2 demonstrated increased PFS compared to patients with the SNP (Median PFS = 16.8 (95% CI=7-26) vs. 7.7 (95% CI=6-9) mos., HR=10.8 (95% CI=2-67), p=0.002). OS and RR were unaffected by the presence of the SNP in all analyses. Conclusions: In this preliminary study, the L1016S SNP in PHLPP2 may be prognostic for poorer PFS in patients with extrapancreatic NETs treated with everolimus. This study is hypothesis generating and requires validation in larger retrospective and randomized, placebo controlled studies in patients with NETs treated with everolimus.

scholarly journals Single-Nucleotide Polymorphism of rs11061971 (+219 A>T) in Adiponectin Receptor 2 (AdipoR2) Gene and Its Association with Risk of Type 2 Diabetes Among an Iranian Population ​

2021 ◽  
Author(s):  
Masoud Tahani ◽  
Mohamad Taghi Goodarzi ◽  
Ali Asghar Ahmadi ◽  
Mohammad Hossein Hasani ◽  
Alireza Farrahi ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Single Nucleotide Polymorphism ◽  
Adiponectin Receptor ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Adiponectin Receptor 2 ◽  
Genetic Modifications ◽  
Significant Difference

Abstract Genetic modifications in the adiponectin receptor 2 (AdipoR2) gene can affect phenotypes associated with insulin resistance and diabetes. The purpose of this study was to evaluate the possible role of genetic modifications in the AdipoR2 gene, to determine the frequency of genotypes and polymorphism alleles of this gene at rs11061971 (+ 219 A > T), and to investigate its correlation with type 2 diabetes (T2D) and its related metabolic profile. In this case-control study, the single-nucleotide polymorphism (SNP) of interest in 116 T2D patients and 102 controls was evaluated using RFLP PCR and FOK 1 enzyme. Fasting blood sugar, cholesterol, triglyceride, insulin, HDL-C, LDL-C and HbA1c were also measured and their correlation with the studied genetic modifications was assessed. The collected data were analyzed using Chi-square test and Hardy-Weinberg equation. There was a significant association in AT and TT genotypes in rs11061971 (+ 219 A > T) with T2D. However, no significant difference was observed in the frequency of alleles between the case and control groups. In addition, in LDL-C and total cholesterol in the control group, there was a significant difference between AA and TT genotypes as well as with AA and AT genotypes. However, no correlation was found between the other serum studied parameters and the genotype of individuals in the rs1106197171 polymorphism. The role of rs11061971 (+ 219 A > T) polymorphism in T2D incidence seems to be strong. This study showed that AT and TT genotypes versus AA genotype increase the risk of diabetes.

Predictive role of single nucleotide polymorphism (rs11614913) in the development of breast cancer in Pakistani population

2020 ◽  
Vol 17 (3) ◽  
pp. 213-227
Author(s):  
Mushtaq Ahmad ◽  
Aftab Ali Shah
Keyword(s):  
Breast Cancer ◽  
Single Nucleotide Polymorphism ◽  
Target Genes ◽  
Amplification Refractory Mutation System ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Significant Difference ◽  
Mutation System ◽  
Predictive Role

Aim: miRNAs play an important role in breast cancer (BC). Variations in miRNAs influence their maturation, expression and consequently regulation of their target genes. Materials & methods: In this study, single nucleotide polymorphism rs11614913 was genotyped in BC patients (n = 300) and 230 controls by employing tetra primer amplification refractory mutation system PCR and Sanger sequencing (Macrogen Korea). Results: A significant difference was observed in the genotypes through co-dominant ( χ2.#x00A0;= 42.03; p < 0.0001), additive (odds ratio [OR] = 0.6441 [0.4887–0.8490, 95% confidence interval]; p < 0.0019), dominant (OR = 0.3996 [0.2809–0.5686], p < 0.0001) and recessive (OR = 0.2993 [0.1220–0.7347], p < 0.009) statistical models showed decreased risk association of C allele with BC. Conclusion: Females having CT genotype are at higher risk of BC as compared with those having CC genotype.

scholarly journals Prevalence of ACSL (rs6552828) polymorphism among runners

2019 ◽  
Vol 24 ◽  
pp. 121-128
Author(s):  
Sigal Ben-Zaken ◽  
Yoav Meckel ◽  
Dan Nemet ◽  
Alon Eliakim
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Genetic Basis ◽  
Maximal Oxygen Consumption ◽  
Professional Athletes ◽  
Distance Runners ◽  
Nucleotide Polymorphism ◽  
Long Distance ◽  
Single Nucleotide ◽  
The Common

The ACSL A/G polymorphism is associated with endurance trainability. Previous studies have demonstrated that homozygotes of the minor AA allele had a reduced maximal oxygen consumption response to training compared to the common GG allele homozygotes, and that the ACSL A/G single nucleotide polymorphism explained 6.1% of the variance in the VO2max response to endurance training. The contribution of ACSL single nucleotide polymorphism to endurance trainability was shown in nonathletes, however, its potential role in professional athletes is not clear. Moreover, the genetic basis to anaerobic trainability is even less studied. Therefore, the aim of the present study was to examine the prevalence of ACSL single nucleotide polymorphism among professional Israeli long distance runners (n=59), middle distance runners (n=31), sprinters and jumpers (n=48) and non-athletic controls (n=60). The main finding of the present study was that the ACSL1 AA genotype, previously shown to be associated with reduced endurance trainability, was not higher among sprinters and jumpers (15%) compared to middle- (16%) and long-distance runners (15%). This suggests that in contrast to previous studies indicating that the ACSL1 single nucleotide polymorphism may influence endurance trainability among non-athletic individuals, the role of this polymorphism among professional athletes is still not clear.

Clinical outcome of patients with follicular lymphoma receiving chemoimmunotherapy in the PRIMA study is not affected by FCGR3A and FCGR2A polymorphisms

Blood ◽  
2012 ◽  
Vol 120 (13) ◽  
pp. 2650-2657 ◽  
Author(s):  
Hervé Ghesquières ◽  
Guillaume Cartron ◽  
John Francis Seymour ◽  
Marie-Hélène Delfau-Larue ◽  
Fritz Offner ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Follicular Lymphoma ◽  
Response Rate ◽  
Single Agent ◽  
Progression Free Survival ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Free Survival ◽  
Rituximab Maintenance

Abstract In patients with follicular lymphoma treated with single-agent rituximab, single nucleotide polymorphisms in the FCGR3A gene are known to influence response and progression-free survival. The prognostic role of FCGR3A and FCGR2A polymorphisms in patients with follicular lymphoma treated with rituximab and chemotherapy combination remains controversial and has not been evaluated in the context of rituximab maintenance. FCGR3A and FCGR2A single nucleotide polymorphisms were evaluated in, respectively, 460 and 455 patients treated in the PRIMA study to investigate whether these were associated with response rate and patient outcome after rituximab chemotherapy induction and 2-year rituximab maintenance. In this representative patient cohort, complete and unconfirmed complete responses after rituximab chemotherapy were observed in 65%, 67%, 66% (P = .86) and 60%, 72%, 66% (P = .21) of FCGR3A VV, VF, FF and FCGR2A HH, HR, RR carriers, respectively. After 2 years of rituximab maintenance (or observation), response rates did not differ among the different genotypes. Progression-free survival measured from either treatment initiation or randomization to observation or maintenance was not influenced by these polymorphisms. These data indicate that FCGR3A and FCGR2A polymorphisms do not influence response rate and outcome when rituximab is combined with chemotherapy or used as maintenance treatment. The PRIMA study is registered at www.clinicaltrials.gov as NCT00140582.

Single-nucleotide Polymorphism in the CD14 Promoter and Periodontal Disease Expression in a Japanese Population

2003 ◽  
Vol 82 (8) ◽  
pp. 612-616 ◽  
Author(s):  
K. Yamazaki ◽  
K. Ueki-Maruyama ◽  
T. Oda ◽  
K. Tabeta ◽  
Y. Shimada ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Periodontal Disease ◽  
Japanese Population ◽  
Young Patients ◽  
Genotype Distribution ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Control Subjects ◽  
Significant Difference ◽  
And Gender

It has been reported that there is a relationship between a single-nucleotide polymorphism (SNP) in the promoter region of the CD14 gene at position -159 (C→T) and infectious diseases. The aim of the present study was to test the hypthesis that expression of this SNP correlates with periodontal disease in a Japanese population. The CD14 genotype was determined in 163 subjects with periodontitis and in 104 age- and gender-matched control subjects without periodontitis. The genotype distribution and allele frequency within the periodontitis patients were not significantly different from those of control subjects. There was, however, a significant difference in the genotype distribution between young patients (< 35 yrs) and older patients (≥ 35 yrs). These findings suggest that CD14 -159C/T polymorphism is not related to the development of periodontitis in a Japanese population, but that, within the periodontitis subjects, expression of the SNP may be related to early disease activity.

scholarly journals Serotonin 5-HT2C Receptor Cys23Ser Single Nucleotide Polymorphism Associates with Receptor Function and Localization In Vitro

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Michelle A. Land ◽  
Holly L. Chapman ◽  
Brionna D. Davis-Reyes ◽  
Daniel E. Felsing ◽  
John A. Allen ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Subcellular Localization ◽  
Cell Lines ◽  
Intracellular Signaling ◽  
Calcium Release ◽  
Wild Type ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Recycling Pathway

Abstract A non-synonymous single nucleotide polymorphism of the human serotonin 5-HT2C receptor (5-HT2CR) gene that converts a cysteine to a serine at amino acid codon 23 (Cys23Ser) appears to impact 5-HT2CR pharmacology at a cellular and systems level. We hypothesized that the Cys23Ser alters 5-HT2CR intracellular signaling via changes in subcellular localization in vitro. Using cell lines stably expressing the wild-type Cys23 or the Ser23 variant, we show that 5-HT evokes intracellular calcium release with decreased potency and peak response in the Ser23 versus the Cys23 cell lines. Biochemical analyses demonstrated lower Ser23 5-HT2CR plasma membrane localization versus the Cys23 5-HT2CR. Subcellular localization studies demonstrated O-linked glycosylation of the Ser23 variant, but not the wild-type Cys23, may be a post-translational mechanism which alters its localization within the Golgi apparatus. Further, both the Cys23 and Ser23 5-HT2CR are present in the recycling pathway with the Ser23 variant having decreased colocalization with the early endosome versus the Cys23 allele. Agonism of the 5-HT2CR causes the Ser23 variant to exit the recycling pathway with no effect on the Cys23 allele. Taken together, the Ser23 variant exhibits a distinct pharmacological and subcellular localization profile versus the wild-type Cys23 allele, which could impact aspects of receptor pharmacology in individuals expressing the Cys23Ser SNP.

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