Strong Association between <i>APOA5</i> Gene Polymorphisms and Hypertriglyceridaemic Episodes

Vrablík, Michal; Hubáček, J. A.; Dlouha, D.; Satny, M.; Adámková, V.; Ceska, R.

doi:10.14712/fb2019065040188

Folia Biologica > Archive > 2019, Vol. 65 > Issue 4 > Strong Association between APOA5…

Fol. Biol. 2019, 65, 188-194

https://doi.org/10.14712/fb2019065040188

Strong Association between APOA5 Gene Polymorphisms and Hypertriglyceridaemic Episodes

Michal Vrablík¹, J. A. Hubáček², D. Dlouha², M. Satny¹, V. Adámková³, R. Ceska¹

¹3rd Department of Internal Medicine, Department of Endocrinology and Metabolism, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic
²Centre for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
³Department of Preventive Cardiology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic

Received May 2019
Accepted May 2019

Plasma triglyceride (TG) levels represent a significant risk factor of cardiovascular and total mortality. Concentrations of TG in the plasma depend, to a large extent, on the genetic background, and the apolipoprotein A5 (APOA5) gene seems to be one of the most powerful players in the plasma TG metabolism regulation. In total, we analysed three tagging APOA5 (rs964184 rs662799, rs3135506) SNPs in 209 patients with plasma TG levels over 10 mmol/l (HTG) on at least one occasion and in 379 treatment-naïve controls (NTG) with plasma TG values within the normal range. Minor alleles of all three analysed APOA5 polymorphisms significantly (all P < 0.0001) increased the risk of hypertriglyceridaemia. The most significant association (P < 0.0000001) was observed for the rs964184 polymorphism, where the minor GG homozygotes had the odds ratio (OR, 95% CI) for hypertriglyceridaemia development 21.30 (8.09-56.07, P < 0.000001) in comparison with the major CC allele homozygotes. Carriers of at least one minor allele at rs3135506 had OR (95% CI) 4.19 (2.75-6.40); (P < 0.000005) for HTG development and similarly, carriers of a minor allele at rs662799 had OR (95% CI) 3.07 (2.00-4.72) (P < 0.0001). The cumulative presence of risk alleles (unweighted gene score) significantly differed between patients with episodes of high TG and controls at P < 0.0000001. There were 73 % of subjects without any of the risk alleles among the controls and 46 % in the patients. In contrast, the controls just included 3 % of subjects with score 3 and more in comparison with 18 % in HTG patients. We conclude that common APOA5 variants are very important genetic determinants of episodic hypertriglyceridaemia in the Czech population with a high potential to be applied in personalized medicine.