scholarly journals Prediction and Structural Comparison of Deleterious Coding Nonsynonymous Single Nucleotide Polymorphisms (nsSNPs) in Human LEP Gene Associated with Obesity

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Hind Bouafi ◽  
Sara Bencheikh ◽  
AL Mehdi Krami ◽  
Imane Morjane ◽  
Hicham Charoute ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Public Health Problem ◽  
Computational Prediction ◽  
The Body ◽  
Structure Stability ◽  
Major Public Health Problem ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Lep Gene ◽  
The Impact

Leptin is a peptide hormone that regulates fat stores in the body and appetite by controlling the feeling of satiety. This hormone is secreted by the white adipose tissue and plays a role in the storage and mobilization of fatty acids. Mutations of the LEP gene have been associated with obesity in different populations; it is a multifactorial disease that constitutes a major public health problem. In this study, we evaluated the impact of missense SNPs in the LEP gene extracted from dbSNP using 8 computational prediction tools. Out of the total of 4337 SNPs, 93 were nsSNPs (nonsynonymous single nucleotide polymorphisms). Among 93 nsSNPs, 12 (S46L, G59S, D61N, D100N, N103K, C117S, D76V, S88C, P90R, I95N, L161R, and R105W) variants were predicted to be the most deleterious by prediction software. On these 12 deleterious SNPs, 8 variants (S46L, G59S, D61N, D100N, N103K, C117S, L161R, and R105W) were located in the conserved positions and showed a decrease in structure stability which was evaluated by I-Mutant and Mupro. Then, by analyzing the different interactions between different amino acids in wild and mutated proteins, we assessed the structural impact of the deleterious modifications using the YASARA software. Among 8 deleterious nsSNPs, we revealed structure changes in the 6 variants S46L, G59S, D100N, L103K, R105W, L161R, two of which R105W, N103K were previously reported as associated with obesity. Our study suggests 6 deleterious mutations could play an important role in contributing to human obesity and worth to be included in association and functional studies, then may be a drug target.

scholarly journals Multiple Infectious Complications in a Severely Injured Patient with Single Nucleotide Polymorphisms in Important Innate Immune Response Genes

2015 ◽  
Vol 9 (1) ◽  
pp. 367-371
Author(s):  
Maarten W.G.A. Bronkhorst ◽  
Peter Patka ◽  
Esther M.M. Van Lieshout
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Public Health Problem ◽  
Injured Patient ◽  
Severe Trauma ◽  
Infectious Complications ◽  
Innate Immune ◽  
Major Public Health Problem ◽  
Trauma Patients ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide

Trauma is a major public health problem worldwide. Infectious complications, sepsis, and multiple organ dysfunction syndrome (MODS) remain important causes for morbidity and mortality in patients who survive the initial trauma. There is increasing evidence for the role of genetic variation in the innate immune system on infectious complications in severe trauma patients. We describe a trauma patient with multiple infectious complications caused by multiple micro-organisms leading to prolonged hospital stay with numerous treatments. This patient had multiple single nucleotide polymorphisms (SNPs) in the MBL2, MASP2, FCN2 and TLR2 genes, most likely contributing to increased susceptibility and severity of infectious disease.

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

scholarly journals Single Nucleotide Polymorphisms in IFN-γ Signaling Pathway Associated with Risk of Hepatitis B Virus Infection in Chinese Children

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Yang Zhuo ◽  
Yalan Yang ◽  
Mingjun Zhang ◽  
Ying Xu ◽  
Zhongping Chen ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Single Nucleotide Polymorphisms ◽  
Signaling Pathway ◽  
Public Health Problem ◽  
Hbv Infection ◽  
Nucleotide Polymorphisms ◽  
Breakthrough Infection ◽  
Single Nucleotide ◽  
B Virus

Hepatitis B virus (HBV) infection is a challenging public health problem in China and worldwide. Mother-to-child transmission is one of the main transmission routes of HBV in highly endemic regions. However, the mechanisms of HBV perinatal transmission in children have not been clearly defined. The aim of this study was to demonstrate the association between single-nucleotide polymorphisms (SNPs) in IFN-γ signaling pathway and HBV infection or breakthrough infection in children. Two hundred and seventy-four HBV-infected children defined as test positive for hepatitis B surface antigen (HBsAg) and 353 controls defined as negative for HBsAg in China were recruited from October 2013 to May 2015. SNPs in IFN-γ signaling pathway including IFNG, IFNGR1, IFNGR2, and IL12B were genotyped. Rs2234711 in IFNGR1 was significantly associated with HBV infection in children (OR = 0.641, 95% CI: 0.450–0.913). In addition, rs2234711 was also significantly associated with HBV breakthrough infection in children born to HBsAg-positive mothers (OR = 0.452, 95% CI: 0.205–0.998). Our study confirmed that genetic variants in IFN-γ signaling pathway have significant associations with HBV infection, especially with HBV breakthrough in children. This study provides insight into HBV infection in children and could be used to help design effective strategies for reducing immunoprophylaxis failure.

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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