Genetic variation in phospholipid transfer protein modulates lipoprotein profiles in hyperalphalipoproteinemia.
We previously demonstrated the role of a phospholipid transfer protein (PLTP) gene variation (rs2294213) in determining levels of high-density lipoprotein cholesterol (HDL-C) in hypoalphalipoproteinemia (HypoA). We have now explored the role of PLTP in hyperalphalipoproteinemia (HyperA). The human PLTP gene was screened for sequence anomalies by DNA melting in 107 subjects with HyperA. The association with plasma lipoprotein levels was evaluated. We detected 7 sequence variations: 1 previously reported variation (rs2294213) and 5 novel mutations including 1 missense mutation (L106F). The PLTP activity was unchanged in the p.L106F mutation. The frequency of the rs2294213 minor allele was markedly increased in the HyperA group (7.0%) in comparison with a control group (4.3%) and the hypoalphalipoproteinemia group (2.2%). Moreover, rs2294213 was strongly associated with HDL-C levels. Linear regression models predict that possession of the rs2294213 minor allele increases HDL-C independent of triglycerides. These findings extend the association of rs2294213 with HDL-C levels into the extremes of the HDL distribution.
Engler
Mary B
MB
Department of Physiological Nursing, University of California San Francisco, San Francisco, CA 94143, USA.
Pullinger
Clive R
CR
Malloy
Mary J
MJ
Natanzon
Yanina
Y
Kulkarni
Medha V
MV
Song
James
J
Eng
Celeste
C
Huuskonen
Jaarko
J
Rivera
Christopher
C
Poon
Annie
A
Bensley
Matt
M
Sehnert
Amy
A
Zellner
Christian
C
Kane
John
J
Aouizerat
Bradley E
BE
D000328:Adult; D000368:Aged; D000818:Animals; D019556:COS Cells; D016022:Case-Control Studies; D002522:Chlorocebus aethiops; D005260:Female; D008040:Genetic Linkage; D014644:Genetic Variation / Q000502:physiology*; D006801:Humans; D006951:Hyperlipoproteinemias / Q000097:blood / Q000235:genetics*; D008074:Lipoproteins / Q000097:blood*; D008075:Lipoproteins, HDL / Q000097:blood*; D008297:Male; D008875:Middle Aged; D049294:Phospholipid Transfer Proteins / Q000235:genetics*; D012189:Retrospective Studies; D014162:Transfection
D008074:Lipoproteins; D008075:Lipoproteins, HDL; D049294:Phospholipid Transfer Proteins