Genomic structure, tissue expression and single nucleotide polymorphisms of lipoprotein lipase and hepatic lipase genes in Chinese perch

2015 ◽  
Vol 22 (4) ◽  
pp. 786-800 ◽  
Author(s):  
L. Li ◽  
X.-F. Liang ◽  
S. He ◽  
J. Sun ◽  
Z.-Y. Wen ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Lipoprotein Lipase ◽  
Hepatic Lipase ◽  
Genomic Structure ◽  
Tissue Expression ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Chinese Perch

Computational analysis and enzyme assay of inhibitor response to disease single nucleotide polymorphisms (SNPs) in lipoprotein lipase

2016 ◽  
Vol 14 (05) ◽  
pp. 1650028 ◽  
Author(s):  
Deyong He ◽  
Ling Huang ◽  
Yaping Xu ◽  
Xiaoliang Pan ◽  
Lijun Liu
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Lipoprotein Lipase ◽  
Active Site ◽  
Complex Structure ◽  
Md Simulations ◽  
Similar Response ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Enzyme Active Site ◽  
Chemical Structures

Lipoprotein lipase (LPL) is the rate-limiting enzyme for the hydrolysis of the triglyceride (TG) core of circulating TG-rich lipoproteins, chylomicrons, and very low-density lipoproteins. The enzyme has been established as an efficacious and safe therapeutic target for the management of obesity. Here, a systematic profile of the lipase inhibitor response of three anti-obesity agents (Orlistat, Lipstatin, and Cetilistat) to clinical LPL missense mutations arising from disease single nucleotide polymorphisms (SNPs) was established by integrating complex structure modeling, virtual mutagenesis, molecular dynamics (MD) simulations, binding energy analysis, and radiolabeled TG hydrolysis assays. The profile was then used to characterize the resistance and sensitivity of systematic mutation–inhibitor pairs. It is suggested that the Orlistat and Lipstatin have a similar response profile to the investigated mutations due to their homologous chemical structures, but exhibit a distinct profile to that of Cetilistat. Most mutations were predicted to have a modest or moderate effect on inhibitor binding; they are located far away from the enzyme active site and thus can only influence the binding limitedly. A number of mutations were found to sensitize or cause resistance for lipase inhibitors by directly interacting with the inhibitor ligands or by indirectly addressing allosteric effect on enzyme active site. Long-term MD simulations revealed a different noncovalent interaction network at the complex interfaces of Orlistat with wild-type LPL as well as its sensitized mutant H163R and resistant mutant I221T.

scholarly journals Evolutionary-genetic analysis of the role of regulatory regions in gene in the formation of the hereditary predisposition structure to preeclampsia in different ethnic groups

2018 ◽  
pp. 32-36
Author(s):  
В.Н. Сереброва ◽  
Е.А. Трифонова ◽  
В.А. Степанов
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Candidate Gene ◽  
Significant Role ◽  
Placental Tissue ◽  
Normal Pregnancy ◽  
Tissue Expression ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Human Pathology

Регуляторные однонуклеотидные полиморфные варианты (rSNP) представляют большой интерес для исследователей, поскольку играют значимую роль в развитии различных патологических состояний человека путем изменения уровня экспрессии кандидатных генов, однако относятся к наименее изученной функциональной группе SNP. Целью данного исследования было изучение генетической компоненты преэклампсии (ПЭ) по системе rSNP нового гена-кандидата NDRG1 и выявление роли естественного отбора в ее формировании. В представленной работе изучено четыре rSNP. Исследование проводилось в различных этнических группах (русские, якуты и буряты). Полученные данные показали ассоциацию с развитием ПЭ трех rSNP гена NDRG1: rs12678229, rs2227262 и rs3802252. Выявлено действие слабого отрицательного отбора для rs2227262. Результаты исследования могут свидетельствовать о значимой роли rSNP нового гена-кандидата NDRG1 в формировании вариабельности уровня экспрессии плацентарной ткани при физиологично протекающей беременности и ПЭ. Regulatory single nucleotide polymorphisms (rSNPs) are of substantial interest, because they play a significant role in the development of human pathology by altering the level of candidate genes expression. However they represent the least studied group of single nucleotide polymorphisms (SNPs). The purpose of this research was to study preeclampsia (PE) genetics components via the regulatory polymorphic variants of the new NDRG1 candidate gene and to detect the role of natural selection in its formation. In this work, we analyzed four rSNPs. Three ethnic group have been studied (Yakut, Russian, Buryat). We have detected significant associations of PE with three rSNPs NDRG1 gene: rs12678229, rs2227262 and rs3802252. We demonstrated the effect of weak negative selection for rs2227262. The results of this study provide evidence for a significant role of the new NDRG1 candidate gene in the variability of the placental tissue expression between normal pregnancy and PE.

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