BACKGROUND: Plasma triglyceride (TG) values are significant predictors of cardiovascular and total mortality. The plasma levels of TGs have an important genetic background. We analyzed whether 32 single nucleotide polymorphisms (SNPs) identified in genome-wide association studies are discriminators of hypertriglyceridemia (HTG) in the Czech population. OBJECTIVES: The objective of this study was to replicate and test the original findings in an independent study and to re-analyze the gene score leading to HTG. METHODS: In total, we analyzed 32 SNPs in 209 patients with plasma TG levels over 10 mmol/L (HTG group) and compared them in a case-control design with 524 treatment-naïve controls (normotriglyceridemic [NTG] group) with plasma TG values below 1.8 mmol/L. RESULTS: Sixteen SNPs were significantly associated with an increased risk of HTG development, with odds ratios (ORs) (95% confidence interval [CI]) varying from 1.40 (1.01-1.95) to 4.69 (3.29-6.68) (rs964184 within the APOA5 gene). Both unweighted (sum of the risk alleles) and weighted gene scores (WGS) (log of the achieved ORs per individual genotype) were calculated, and both gene scores were significantly different between groups. The mean score of the risk alleles was significantly increased in the HTG group compared to the NTG group (18.5 ± 2.5 vs. 15.7 ± 2.3, respectively; P < 0.00001). Subjects with a WGS over 9 were significantly more common in the HTG group (44.5%) than in the NTG group, in which such a high score was observed in only 4.7% of subjects (OR 16.3, 95% CI 10.0-36.7; P < 0.0000001). CONCLUSIONS: An increased number of risk genetic variants, calculated both in a weighted or unweighted manner, significantly discriminates between the subjects with HTG and controls. Population-specific sets of SNPs included into the gene score seem to yield better discrimination power.

• MeSH
• alely MeSH
• genetická predispozice k nemoci * MeSH
• genetické asociační studie * metody   MeSH
• genetické testování MeSH
• genotyp MeSH
• hypertriglyceridemie krev   diagnóza   epidemiologie   genetika   MeSH
• jednonukleotidový polymorfismus MeSH
• komorbidita MeSH
• lidé středního věku MeSH
• lidé MeSH
• odds ratio MeSH
• senioři MeSH
• studie případů a kontrol 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
• Geografické názvy
• Česká republika epidemiologie   MeSH

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