title: Rare APOA5 promoter variants associated with paradoxical HDL cholesterol decrease in response to fenofibric acid therapy.
abstract: Individuals with mixed dyslipidemia, including high triglycerides (TGs) and low high density lipoprotein cholesterol (HDL-C), have increased risk for coronary events. We examined the effect of rare genetic variants in the APOA5 gene region on plasma HDL-C, apolipoprotein A-I (apoA-I), and TG response to fenofibric acid monotherapy and in combination with statins. The APOA5 gene region was sequenced in 1,612 individuals with mixed dyslipidemia in a randomized trial of fenofibric acid alone and in combination with statins. Student's t-test and rare variant burden tests were used to examine plasma HDL-C, apoA-I, and TG response. Rare APOA5 promoter region variants were associated with decreased HDL-C and apoA-I levels in response to fenofibric acid therapy; rare missense variants were associated with increased TG response to combination therapy. Further study is needed to examine the effect of these rare variants on coronary outcomes in this population in response to fenofibric acid monotherapy or combined with statins.
authors: Center for Human Genetics, Marshfield Clinic Research Foundation, Marshfield, WI, USA. brautbar@bcm.edu
authors: Ariel
authors: A
authors: Brautbar
authors: Maja
authors: M
authors: Barbalic
authors: Fengju
authors: F
authors: Chen
authors: John
authors: J
authors: Belmont
authors: Salim S
authors: SS
authors: Virani
authors: Steve
authors: S
authors: Scherer
authors: Robert A
authors: RA
authors: Hegele
authors: Christie M
authors: CM
authors: Ballantyne
mesh_terms: D000596:Amino Acids / Q000494:pharmacology; D016632:Apolipoprotein A-I / Q000097:blood; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A / Q000235:genetics*; D008076:Cholesterol, HDL / Q000097:blood*; D050171:Dyslipidemias / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D011345:Fenofibrate / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D008297:Male; D011401:Promoter Regions, Genetic / Q000235:genetics*; D014280:Triglycerides / Q000097:blood
chemical_list: C437704:APOA5 protein, human; D000596:Amino Acids; D016632:Apolipoprotein A-I; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A; D008076:Cholesterol, HDL; D014280:Triglycerides; C006012:fenofibric acid; D011345:Fenofibrate; C013165:statine
keywords: apolipoproteins; cholesterol-lowering drugs; fenofibric acid; high density lipoprotein; lipids; rare variants
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