Interactions between hepatic lipase and apolipoprotein E gene polymorphisms affect serum lipid profiles of healthy Canadian adults

Authors: Wood, Kevin C.M.; Fullerton, Morgan D.; El-Sohemy, Ahmed; Bakovic, Marica

Source: Applied Physiology, Nutrition, and Metabolism, Volume 33, Number 4, 1 August 2008 , pp. 761-768(8)

Publisher: NRC Research Press

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Abstract:

The purpose of this study was to assess the individual and interactive effects between hepatic lipase (LIPC; C-514T, G-250A) and apolipoprotein E (APOE) (E2, E3, E4) gene polymorphisms on levels of plasma lipoprotein cholesterol and triglyceride among healthy, young, Canadian adults (n = 440). All subjects with at least one APOE2 allele had significantly lower low-density lipoprotein cholesterol, total cholesterol, and total cholesterol - high-density lipoprotein cholesterol ratio when compared with those with the APOE3 or APOE4 allele. There were significant differences in the LIPC allele and genotype frequencies between Caucasian (n = 207) and Asian (n = 211) individuals, but ethnicity did not contribute to the variations in circulating lipids. In addition, the lowest triglyceride levels (0.87 ± 0.27 mmol·mL-1) were found in all APOE2 individuals carrying LIPC-514-CC and LIPC-250-GG genotypes, whereas the highest triglyceride levels (1.29 ± 0.34 -1.32 ± 0.32 mmol·mL-1) were found in APOE2 individuals carrying the opposite genotypes, LIPC-514TT and LIPC-250AA. These observations, distinct from the anti-atherogenic effects of APOE2 through the lowering of low-density lipoprotein cholesterol and LIPC on high-density lipoprotein cholesterol, suggest that there is an interactive effect between APOE and LIPC genotypes on plasma triglyceride levels. These results provide the basis for further studies on establishing which genotype combinations would be the most protective against hypertriglyceridemia.

Cette étude se propose d'analyser chez 440 jeunes Canadiens en bonne santé les effets individuels et interactifs des diverses formes du gène de la lipase hépatique (LIPC) (C-514T, G-250A) et de celui de l'apoprotéine E (APOE2, E3, E4) sur les concentrations plasmatiques de triglycérides et de cholestérol associées aux lipoprotéines. Comparativement aux individus présentant des allèles APOE3 ou APOE4, tous les sujets présentant au moins un allèle APOE2 ont une plus faible concentration de LDL-cholestérol, moins de cholestérol total et un plus faible ratio cholestérol total - HDL-cholestérol. On observe des différences significatives entre les fréquences des allèles LIPC et des génotypes des Caucasiens (n = 207) et des Asiatiques (n = 211), mais l'ethnicité n'explique pas les variations des concentrations de lipides dans la circulation. En outre, on observe les plus faibles taux de triglycérides (0,87 ± 0,27 mmol·mL-1) chez tous les sujets portant l'allèle APOE2 dans les génotypes LIPC-514-CC et LIPC-250-GG et les plus forts taux (1,29 ± 0,34 -1,32 ± 0,32 mmol·mL-1) chez les sujets portant l'allèle APOE2 mais identifiés aux génotypes opposés, LIPC-514TT et LIPC-250AA. Ces observations qui se démarquent des effets anti-athérogènes de APOE2 et de LIPC sur la diminution respective des concentrations de LDL-cholestérol et de HDL-cholestérol suggèrent une interaction des génotypes APOE et LIPC quant aux taux plasmatiques de triglycérides. Ces résultats constituent la base pour de nouvelles études sur les meilleures combinaisons de génotypes à des fins de lutte contre l'hypertriglycéridémie.

Document Type: Research article

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