Inherited Apolipoprotein A-V Deficiency in Severe Hypertriglyceridemia

Abstract

Objective-Mutations in LPL or APOC2 genes are recognized causes of inherited forms of severe hypertriglyceridemia.However, some hypertrigliceridemic patients do not have mutations in either of these genes. Because inactivation or hyperexpression of APOA5 gene, encoding apolipoprotein A-V (apoA-V), causes a marked increase or decrease of plasma triglycerides in mice, and because some common polymorphisms of this gene affect plasma triglycerides in humans, we have hypothesized that loss of function mutations in APOA5 gene might cause hypertriglyceridemia. Methods and Results-We sequenced APOA5 gene in 10 hypertriglyceridemic patients in whom mutations in LPL and APOC2 genes had been excluded. One of them was found to be homozygous for a mutation in APOA5 gene (c.433 CϾT, Q145X), predicted to generate a truncated apoA-V devoid of key functional domains. The plasma of this patient was found to activate LPL in vitro less efficiently than control plasma, thus suggesting that apoA-V might be an activator of LPL. Ten carriers of Q145X mutation were found in the patient's family; 5 of them had mild hypertriglyceridemia. Conclusions-As

Apolipoprotein AV does not contribute to hypertriglyceridaemia or triglyceride lowering by dietary fish oil and rosiglitazone in obese Zucker rats

“…In humans with hypertriglyceridaemia or familial combined hyperlipidaemia, polymorphisms in APOA5 show a strong association with plasma triglyceride levels across several ethnic groups [2][3][4]39]. ApoAV deficiency leads to severe hypertriglyceridaemia [40,41]. Recent measurements of plasma apoAV in normolipaemic subjects revealed a weak negative correlation [35,36] or a tendency towards a positive correlation of plasma apoAV and triglycerides (F. G. Schaap et al, unpublished results).…”

Protease Inhibitor-Associated Dyslipidemia in HIV-Infected Patients Is Strongly Influenced by the APOA5–1131T→C Gene Variation

“…Its exact function has not been completely elucidated, but the available data indicate that it modulates TG metabolism by controlling production of VLDL and catabolism of the lipolysis of TG-rich lipoproteins (10 ). The latter role has been confirmed not only in vitro but also in patients who develop severe hypertriglyceridemia attributable to apo A-V deficiency (11 ).…”

Validating a Rapid Method for Detecting Common Polymorphisms in the APOA5 Gene by Melting Curve Analysis Using LightTyper

“…The recently identified apolipoprotein A-V gene (APOA5) has been shown to play an important role in hypertriglyceridemia (1 ). Genetic variation in APOA5 has been consistently associated with plasma triglyceride concentrations in several studies (2)(3)(4).…”