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- Title
The minor allele of the missense polymorphism Ser251Pro in perilipin 2 (PLIN2) disrupts an α-helix, affects lipolysis, and is associated with reduced plasma triglyceride concentration in humans.
- Authors
Magné, Joiölle; Aminoff, Anna; Sundelin, Jeanna Perman; Mannila, Maria Nastase; Gustafsson, Peter; Hultenby, Kiell; Wernerson, Annika; Bauer, Greta; Listenberger, Laura; Neville, Matt J.; Karpe, Fredrik; Borén, Jan; Ehrenborg, Ewa
- Abstract
Pefilipin 2 (PLIN2) is the most abunda lipid droplet (LD)-associated protein in nonadipose tissue, and its expression correlates with intracellular lipid accumulation. Here we identified a missens 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 α-helix in PIXq2 Analyses of macrophages from individuals carrying Ser251Pro variants and human embryonic kidney 29 (HEK293) cells stably transfected with either of the alleles demonstrated that the Pro251 variant caus increased lipid accumulation and decreased fipolysis 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 an very low-density lipoprotein concentrations. Altogether, these data provide the first evidence of a polymorphis in PLIN2 that affects PLIN2 function and may influence the development of metabolic and cardiovascular diseases.
- Subjects
PERILIPIN; LIPOPROTEINS; MISSENSE mutation; KIDNEY cell culture; CARDIOVASCULAR diseases risk factors
- Publication
FASEB Journal, 2013, Vol 27, Issue 8, p3090
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fj.13-228759