Nejvíce citovaný článek - PubMed ID 16176166
Apolipoprotein A5 and triglyceridemia. Focus on the effects of the common variants
Apolipoprotein A5 (APOA5) is a small protein, expressed predominantly in the liver. In plasma, it is located on triglyceride rich lipoprotein particles (chylomicrones and VLDL) and on HDL. Plasma concentration of apolipoprotein A5 is very low, suggesting rather regulatory (activation of lipoprotein lipase, …) than structural function. APOA5 is an important determinant of plasma triglyceride concentration; this effect has been confirmed both on animal models, as well as on human studies. Minor alleles of three commonly analysed variants within this gene (rs662799, rs3135506, rs2075291) are associated with higher plasma TG values and increased risk of myocardial infarction, with some important interethnic differences observed. Further roles of APOA5; determination of BMI, diabetes and last but not least nutri- and pharmaco-genetic interactions are suggested, but without the definitive conclusions.
- Klíčová slova
- Apolipoprotein A5, Cardiovascular disease, Polymorphism, Triglycerides,
- MeSH
- apolipoprotein A-V krev genetika metabolismus MeSH
- jednonukleotidový polymorfismus * MeSH
- kardiovaskulární nemoci krev epidemiologie genetika MeSH
- lidé MeSH
- triglyceridy krev MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- APOA5 protein, human MeSH Prohlížeč
- apolipoprotein A-V MeSH
- triglyceridy MeSH
BACKGROUND AND AIMS: Several smaller studies reported interactions between dietary factors and apolipoprotein A5 (APOA5) gene polymorphisms in determination of plasma lipids. We tested interactions between APOA5 haplotypes and dietary intake in determination of plasma triglycerides (TG) and other lipids. METHODS AND RESULTS: Participants (5487 males and females aged 45-69) were classified according to the number (0, 1, 2+) of minor APOA5 alleles (using T-1131 > C; rs662799 and Ser19 > Trp; rs3135506 polymorphisms) and into three groups of low (bottom 25%), medium (26th-75th percentile) and high (top 25%) of intake of total energy and total, saturated and polyunsaturated fats, assessed by food frequency questionnaire. The age-sex adjusted geometric means of plasma TG increased with the number of minor alleles, from 1.57 (standard error 0.01), to 1.79 (0.02) to 2.29 (0.10) mmol/L (p < 0.00001) but TG did not differ between groups with low, medium and high total energy intake (p = 0.251). TG concentrations were highest in subjects with the combination of 2+ minor alleles and the highest energy intake (mean 2.59 [0.19], compared with 1.62 [0.03] in subjects with lowest energy intake and no minor allele) but the interaction between energy intake and APOA5 haplotypes was not statistically significant (p = 0.186). Analogous analyses with total, saturated and polyunsaturated fat intake yielded similar nonsignificant results. Effects of APOA5 and dietary intakes on total and HDL cholesterol were weaker and no interactions were significant. CONCLUSION: In this Slavic Caucasian population sample, we did not detect the hypothesized interaction between common SNPs within the APOA5 gene and diet in determination of blood lipids.
- Klíčová slova
- Apolipoprotein A5, Interaction, Polymorphism, Total energy intake, Triglycerides,
- MeSH
- alely MeSH
- apolipoprotein A-V MeSH
- apolipoproteiny A genetika MeSH
- běloši MeSH
- cholesterol krev MeSH
- dietní tuky aplikace a dávkování MeSH
- energetický příjem * MeSH
- haplotypy * MeSH
- hodnocení stavu výživy MeSH
- index tělesné hmotnosti MeSH
- jednonukleotidový polymorfismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- lineární modely MeSH
- průzkumy a dotazníky MeSH
- senioři MeSH
- triglyceridy krev MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Geografické názvy
- Česká republika MeSH
- Názvy látek
- APOA5 protein, human MeSH Prohlížeč
- apolipoprotein A-V MeSH
- apolipoproteiny A MeSH
- cholesterol MeSH
- dietní tuky MeSH
- triglyceridy MeSH
BACKGROUND: The importance of apolipoprotein A-V (APOAV) gene variants in the determination of plasma triglyceride levels in humans has been proven in several population studies. OBJECTIVES: To investigate whether APOAV gene variants are associated with the different plasma cholesterol fractions. METHODS: The influence of APOAV polymorphisms (T-1131>C, Ser19>Trp and Val153>Met) on plasma cholesterol fractions was evaluated in 1191 men and 1368 women representatively selected from the Czech population. Low-density lipoprotein cholesterol, non-high-density lipoprotein (non-HDL) cholesterol and HDL cholesterol levels were analyzed. RESULTS: The T-1131>C variation in the APOAV gene was found to affect plasma non-HDL cholesterol, showing significantly higher levels in C-1131 carriers than in T/T-1131 homozygotes. This association was observed in both men (4.61+/-1.09 mmol/L in C-1131 carriers versus 4.47+/-1.07 mmol/L in T/T-1131 homozygotes; P<0.01) and women (4.46+/-1.22 mmol/L in C-1131 carriers versus 4.24+/-1.17 mmol/L in T/T-1131 homozygotes; P<0.01). Interestingly, when low-density lipoprotein cholesterol (obtained by the Friedewald formula) or HDL cholesterol levels were analyzed, no significant association was detected. CONCLUSION: The APOAV gene variant T-1131>C may play a role not just in the genetic determination of triglyceride levels but may also influence plasma levels of non-HDL cholesterol.
- Klíčová slova
- Apolipoprotein A-V, Non-HDL cholesterol, Polymorphism, Triglycerides,
- Publikační typ
- časopisecké články MeSH