Open AccessA promoter variant of the APOA5 gene increases atherogenic LDL levels and arterial stiffness in hypertriglyceridemic patients
Author(s) -
Minjoo Kim,
Hye Jin Yoo,
Eunji Lee,
Jey Sook Chae,
Sang Hyun Lee,
Jong Ho Lee
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0186693
Subject(s) - medicine , hypertriglyceridemia , endocrinology , triglyceride , population , arterial stiffness , single nucleotide polymorphism , apolipoprotein b , biology , cholesterol , genotype , genetics , gene , blood pressure , environmental health
Hypertriglyceridemia is recognized as an independent risk factor for coronary artery disease. The apolipoprotein A5 gene ( APOA5 ) is a key regulator of triglyceride levels. We aimed to evaluate the associations of single nucleotide polymorphisms (SNPs) in APOA5 , including -1131T>C and c.553G>T, with hypertriglyceridemia, apoA5 concentrations, atherogenic LDL cholesterol levels, and arterial stiffness in hypertriglyceridemic patients. The study population included 599 hypertriglyceridemic patients (case) and 1,549 untreated normotriglyceridemic subjects (control). We genotyped two APOA5 variants, -1131T>C (rs662799) and c.553G>T (rs2075291). The frequencies of the CC genotype of -1131T>C (0.165) and the T allele of c.553G>T (0.119) were significantly higher in hypertriglyceridemic patients than in normotriglyceridemic subjects (0.061 and 0.070, respectively; all p <0.001). In the control and case groups, both the -1131T>C and c.553G>T variants were associated with higher triglyceride and lower HDL cholesterol levels. Controls with the -1131CC variant had lower apoA5 concentrations than controls with the -1131TT variant. Similar effects of the -1131T>C variant on apoA5 were observed in the cases. In the hypertriglyceridemic group, the -1131T>C variant was associated with a smaller LDL particle size, higher levels of oxidized LDL and malondialdehyde, and higher brachial-ankle pulse wave velocity. The -1131T>C and c.553G>T polymorphisms were associated with hypertriglyceridemia in the study population, but only the -1131T>C polymorphism directly affected apoA5 concentrations. Hypertriglyceridemic patients carrying the APOA5 -1131T>C polymorphism exhibited increased atherogenic LDL levels and arterial stiffness, probably due to an effect of the -1131T>C polymorphism on apoA5 concentrations.