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The minor allele of...
The minor allele of the missense polymorphism Ser251Pro in perilipin 2 (PLIN2) disrupts an alpha-helix, affects lipolysis, and is associated with reduced plasma triglyceride concentration in humans
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Magne, J. (author)
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- Aminoff, A. (author)
- Karolinska Institutet
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- Perman Sundelin, Jeanna (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
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- Mannila, M. N. (author)
- Karolinska Institutet
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- Gustafsson, P. (author)
- Karolinska Institutet
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- Hultenby, K. (author)
- Karolinska Institutet
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Wernerson, A. (author)
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Bauer, G. (author)
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Listenberger, L. (author)
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Neville, M. J. (author)
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Karpe, F. (author)
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- Borén, Jan, 1963 (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
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- Ehrenborg, E. (author)
- Karolinska Institutet
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(creator_code:org_t)
- 2013-04-19
- 2013
- English.
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In: Faseb Journal. - : Wiley. - 0892-6638 .- 1530-6860. ; 27:8, s. 3090-3099
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Perilipin 2 (PLIN2) is the most abundant lipid droplet (LD)-associated protein in nonadipose tissue, and its expression correlates with intracellular lipid accumulation. Here we identified a missense polymorphism, Ser251Pro, that has major effect on protein structure and function, along with an influence on human plasma triglyceride concentration. The evolutionarily conserved Ser251Pro polymorphism was identified with the ClustalW program. Structure modeling using 3D-JigSaw and the Chimera package revealed that the Pro251 allele disrupts a predicted -helix in PLIN2. Analyses of macrophages from individuals carrying Ser251Pro variants and human embryonic kidney 293 (HEK293) cells stably transfected with either of the alleles demonstrated that the Pro251 variant causes increased lipid accumulation and decreased lipolysis. Analysis of LD size distribution in stably transfected cells showed that the minor Pro251 allele resulted in an increased number of small LDs per cell and increased perilipin 3 protein expression levels as compared with cells carrying the major Ser251 allele. Genotyping of 2113 individuals indicated that the Pro251 variant is associated with decreased plasma triglyceride and very low-density lipoprotein concentrations. Altogether, these data provide the first evidence of a polymorphism in PLIN2 that affects PLIN2 function and may influence the development of metabolic and cardiovascular diseases.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Keyword
- lipid droplets
- lipid accumulation
- lipid metabolism
- HEK293 cells
- macrophages
- differentiation-related protein
- cytosolic lipid droplets
- low-density-lipoprotein
- human macrophages
- insulin sensitivity
- foam
- cell
- high-risk
- metabolism
- secretion
- tip47
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Magne, J.
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Aminoff, A.
-
Perman Sundelin, ...
-
Mannila, M. N.
-
Gustafsson, P.
-
Hultenby, K.
-
show more...
-
Wernerson, A.
-
Bauer, G.
-
Listenberger, L.
-
Neville, M. J.
-
Karpe, F.
-
Borén, Jan, 1963
-
Ehrenborg, E.
-
show less...
- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Biochemistry and ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
- Articles in the publication
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Faseb Journal
- By the university
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University of Gothenburg
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Karolinska Institutet