Lipoprotein (a) as a marker of hereditary lipid metabolism disorders in patients with early manifestation of coronary artery disease

Abstract

Background: The clinical phenotype of familial hypercholesterolemia (FH) combined with the “classical” genetic defects of this disease increase the risk of coronary artery disease (CAD) in the case of a high level of lipoprotein (a) (Lp(a)).

Aim: To assess the association of hereditary disorders of lipid metabolism with a high level of Lp(a) in the case of an early manifestation of CAD in the absence of the FH phenotype.

Methods: We studied 81 patients with premature CAD (at the age up to 55 years in men and up to 60 years in women). Lp(a) was measured in the blood serum by the immunoturbidimetric method. We performed the molecular genetic testing, using massively parallel sequencing, which included the following panel of genes: ABCA1, ABCG1, ABCG5, ABCG8, ANGPTL3, APOA1, APOA2, APOA4, APOA5, APOB, APOC1, APOC2, APOC3, APOE, APOH, CETP, CH25H, CIDEC, CREB3L3, GPD1, GPIHBP1, LCAT, LDLR, LDLRAP1, LIPA, LIPC, LIPE, LIPG, LMF1, LPA, LPL, MTTP, MYLIP, NPC1, NPC1L1, NPC2, PCSK9, PLTP, PPP1R17, SAR1B, SCARB1, STAP1.

Results: 24 (29.6%) patients had Lp(a) ≥ 30 mg/dl and were more likely to have a family history of CAD (70.8% vs 42.1%, p=0.05). In patients with a confirmed FH phenotype, there were no pathogenic variants associated with hereditary disorders of lipid metabolism. 4 patients with Lp(a) ≥30 mg/dl without a confirmed FH phenotype appeared to be carriers of pathogenic variants in the genes of lipid metabolism (LDLR p.Glu763Asp, ABCA1 p.Arg1128His, APOA5 p.His321Le), as well as of a not previously registered variant in the LIPE gene NM_005357.4:c. 2312T>C.

Conclusions: Lp(a) can be an appropriate marker for revealing pathogenic variants in the genes of the lipid metabolism system in patients without the clinical FH phenotype with an early CAD manifestation.

Keywords

lipoprotein(a) / coronary heart disease / genetic testing / lipid metabolism disorders / massively parallel sequencing

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Funding

Минобрнауки РоссииMinistry of Science and Higher Education of the Russian Federation

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