scholarly journals ParkinExon Rearrangements and Sequence Variants inLRRK2Mutations Carriers: Analysis on a Possible Modifier Effect onLRRK2Penetrance

2010 ◽  
Vol 2010 ◽  
pp. 1-5 ◽  
Author(s):  
Paolo Solla ◽  
Antonino Cannas ◽  
Gianluca Floris ◽  
Maria Rita Murru ◽  
Daniela Corongiu ◽  
...  
Keyword(s):  
Environmental Factors ◽  
Single Nucleotide Polymorphisms ◽  
Family Members ◽  
Gene Mutations ◽  
Sequence Variants ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Mutation Carriers ◽  
Common Causes ◽  
Modifier Effect

Mutations inLRRK2represent the most common causes of Parkinson's disease (PD) identified to date, but their penetrance is incomplete and probably due to the presence of other genetic or environmental factors required for development of the disease. We analyzed the presence ofparkinsequence variants (mutations or polymorphisms) and exon rearrangements inLRRK2mutations carriers (both PD patients and unaffected relatives) in order to detect a possible modifier effect on penetrance. Eight families with nine PD patients with heterozygousLRRK2mutations (identified within 380 Sardinian PD patients screened for the presence of the five most commonLRRK2mutations) and sixteen additional relatives were genetically investigated for the presence ofLRRK2andparkinmutations. No evidence was found for the presence of pathologicalparkinmutations or exon rearrangements in patients or not affected family members. Three single-nucleotide polymorphisms (SNPs) were identified both in patients and unaffected relatives but did not significantly differ between the two groups. These data provide no support to the hypothesis whereby suchparkingene mutations may be commonly implicated in possible effect on penetrance inLRRK2mutation carriers.

Statin-induced adverse effects – facts and genes

2013 ◽  
Vol 154 (3) ◽  
pp. 83-92
Author(s):  
Mariann Harangi ◽  
Noémi Zsíros ◽  
Lilla Juhász ◽  
György Paragh
Keyword(s):  
Risk Factors ◽  
Single Nucleotide Polymorphisms ◽  
Adverse Effects ◽  
Adverse Events ◽  
Statin Therapy ◽  
Significant Proportion ◽  
Gene Mutations ◽  
Nucleotide Polymorphisms ◽  
Serious Adverse Events ◽  
Single Nucleotide

Statin therapy is considered to be safe and rarely associated with serious adverse events. However, a significant proportion of patients on statin therapy show some degree of intolerance which can lead to decreased adherence to statin therapy. The authors summarize the symptoms, signs and frequencies of the most common statin-induced adverse effects and their most important risk factors including some single nucleotide polymorphisms and gene mutations. Also, they review the available approaches to detect and manage the statin-intolerant patients. Orv. Hetil., 2013, 154, 83–92.

scholarly journals Progranulin Levels in Plasma and Cerebrospinal Fluid in Granulin Mutation Carriers

2016 ◽  
Vol 6 (2) ◽  
pp. 330-340 ◽  
Author(s):  
Lieke H.H. Meeter ◽  
Holger Patzke ◽  
Gordon Loewen ◽  
Elise G.P. Dopper ◽  
Yolande A.L. Pijnenburg ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Single Nucleotide Polymorphisms ◽  
Frontotemporal Dementia ◽  
Coefficient Of Variation ◽  
Treatment Monitoring ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Therapeutic Trials ◽  
Mutation Carriers ◽  
Pathogenic Mutations

Background: Pathogenic mutations in the granulin gene (GRN) are causative in 5-10% of patients with frontotemporal dementia (FTD), mostly leading to reduced progranulin protein (PGRN) levels. Upcoming therapeutic trials focus on enhancing PGRN levels. Methods: Fluctuations in plasma PGRN (n = 41) and its relationship with cerebrospinal fluid (CSF, n = 32) and specific single nucleotide polymorphisms were investigated in pre- and symptomatic GRN mutation carriers and controls. Results: Plasma PGRN levels were lower in carriers than in controls and showed a mean coefficient of variation of 5.3% in carriers over 1 week. Although plasma PGRN correlated with CSF PGRN in carriers (r = 0.54, p = 0.02), plasma only explained 29% of the variability in CSF PGRN. rs5848, rs646776 and rs1990622 genotypes only partly explained the variability of PGRN levels between subjects. Conclusions: Plasma PGRN is relatively stable over 1 week and therefore seems suitable for treatment monitoring of PGRN-enhancing agents. Since plasma PGRN only moderately correlated with CSF PGRN, CSF sampling will additionally be needed in therapeutic trials.

Combined Effects of Single Nucleotide Polymorphisms (SNPs) within C-reactive Protein (CRP) and Environmental Parameters on Risk and Prognosis for Diabetic Foot Osteomyelitis Patients

2020 ◽  
Vol 128 (08) ◽  
pp. 528-539
Author(s):  
Shanjin Wang ◽  
Haowei Xu ◽  
Ningfeng Zhou ◽  
Weidong Zhao ◽  
Desheng Wu ◽  
...  
Keyword(s):  
Environmental Factors ◽  
Single Nucleotide Polymorphisms ◽  
Diabetic Foot ◽  
Environmental Parameters ◽  
Combined Effects ◽  
Nucleotide Polymorphisms ◽  
C Reactive Protein ◽  
Single Nucleotide ◽  
Reactive Protein ◽  
Diabetic Foot Osteomyelitis

Abstract Purpose This study was aimed to discover the combined effects of single nucleotide polymorphisms (SNPs) within the C-reactive protein (CRP) gene and potential environmental factors on the risk and prognosis for diabetic foot osteomyelitis (DFO). Methods A total of 1734 diabetes mellitus patients, 681 with DFO and 1053 without DFO, were successfully recruited, as well as 1261 healthy control individuals. Participants data were recorded regarding age, gender, smoking and drinking history, body mass index (BMI), hypertension, cacosmia, and ulceration. A total of 11 SNPs within the CRP gene were designated for exploration, by logistic regression analyses, of how they might interact with environmental factors to affect susceptibility to DFO. Results Frequencies of smoking and drinking, and incidence of hypertension, cacosmia, or ulceration displayed marked differences (all P<0.05) between DFO and non-DFO patients. Furthermore, allele G of rs11265260 (A>G), allele G of rs1800947 (C>G), and allele T of rs3093059 (T>C) and rs1130864 (C>T) exhibited a trend to increase risk of DFO (all P<0.05). Allele G of rs11265260 (A>G), allele G of rs1800947 (C>G) and rs3093068 (G>C), and allele T of rs1130864 (C>T) were significant predictors of poor prognosis among DFO patients (P<0.05). In addition, genotypes of rs11265260 (i.e., GG and AG), rs1800947 (i.e., CG and GG), rs3093059 (i.e., TT) and rs113084 (i.e., CT and TT) amplified the influence of smoking, alcohol consumption, cacosmia, and ulceration on progression from non-DFO to DFO (all γ>1). Conclusion Genetic mutations within CRP functioned interactively with external factors to affect DFO risk.

scholarly journals Impacts of Nonsynonymous Single Nucleotide Polymorphisms of Adiponectin Receptor 1 Gene on Corresponding Protein Stability: A Computational Approach

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Md. Abu Saleh ◽  
Md. Solayman ◽  
Sudip Paul ◽  
Moumoni Saha ◽  
Md. Ibrahim Khalil ◽  
...  
Keyword(s):  
Free Energy ◽  
Single Nucleotide Polymorphisms ◽  
Metabolic Diseases ◽  
Gene Mutations ◽  
Adiponectin Receptor ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Adiponectin Receptor 1 ◽  
Structural Impacts ◽  
Dbsnp Database

Despite the reported association of adiponectin receptor 1 (ADIPOR1)gene mutations with vulnerability to several human metabolic diseases, there is lack of computational analysis on the functional and structural impacts of single nucleotide polymorphisms (SNPs) of the humanADIPOR1at protein level. Therefore, sequence- and structure-based computational tools were employed in this study to functionally and structurally characterize the coding nsSNPs ofADIPOR1gene listed in the dbSNP database. Ourin silicoanalysis by SIFT, nsSNPAnalyzer, PolyPhen-2, Fathmm, I-Mutant 2.0, SNPs&GO, PhD-SNP, PANTHER, and SNPeffect tools identified the nsSNPs with distorting functional impacts, namely, rs765425383 (A348G), rs752071352 (H341Y), rs759555652 (R324L), rs200326086 (L224F), and rs766267373 (L143P) from 74 nsSNPs ofADIPOR1gene. Finally the aforementioned five deleterious nsSNPs were introduced using Swiss-PDB Viewer package within the X-ray crystal structure of ADIPOR1 protein, and changes in free energy for these mutations were computed. Although increased free energy was observed for all the mutants, the nsSNP H341Y caused the highest energy increase amongst all. RMSD and TM scores predicted that mutants were structurally similar to wild type protein. Our analyses suggested that the aforementioned variants especially H341Y could directly or indirectly destabilize the amino acid interactions and hydrogen bonding networks of ADIPOR1.

Analyses of Sequence Variants in theMYOCGene and of Single Nucleotide Polymorphisms in theNR3C1andFKBP5Genes in Corticosteroid-Induced Ocular Hypertension

2015 ◽  
Vol 36 (4) ◽  
pp. 299-302 ◽  
Author(s):  
Barend F. Hogewind ◽  
Shazia Micheal ◽  
Frederieke E. Schoenmaker-Koller ◽  
Carel B. Hoyng ◽  
Anneke I. den Hollander
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Ocular Hypertension ◽  
Sequence Variants ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide

ACTN4 Gene Mutations and Single Nucleotide Polymorphisms in Idiopathic Focal Segmental Glomerulosclerosis

2009 ◽  
Vol 111 (2) ◽  
pp. c87-c94 ◽  
Author(s):  
Shengchuan Dai ◽  
Zhaohui Wang ◽  
Xiaoxia Pan ◽  
Xiaonong Chen ◽  
Weiming Wang ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Focal Segmental Glomerulosclerosis ◽  
Gene Mutations ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Segmental Glomerulosclerosis

Development of a simple method for the determination of single nucleotide polymorphisms

2010 ◽  
Vol 34 (8) ◽  
pp. S75-S75
Author(s):  
Weifeng Zhu ◽  
Zhuoqi Liu ◽  
Daya Luo ◽  
Xinyao Wu ◽  
Fusheng Wan
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Nucleotide Polymorphisms ◽  
Simple Method ◽  
Single Nucleotide
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