Hypertriglyceridemia (Hypertriglyceridemia) - Genes APOA5, APOC2, LIPI LMF1, GPIHBP1, LPL.  

Elevated blood triglycerides (hypertriglyceridemia), can be caused by various genetic alterations. Several genes (APOA5, APOC2, LIPI LMF1, GPIHBP1, LPL) encoding enzymes degrading lipids, proteins activators of enzymes with lipase or transport proteins fats in the body, which mutations can lead to increased triglycerides. The major organic disorders caused by increased triglycerides are the appearance of cutaneous xanthoma, pancreatitis, coronary heart disease (heart attacks) , and stroke.

Mutations in some genes have been correlated with some well characterized from clinically processes such as hyperlipoproteinemia 1B (HLPP1B: Hyperlipoproteinemia 1B) (APOC2 gene), hyperlipoproteinemia type 1D (HLPP1D: Hyperlipoproteinemia 1D) (GPIHBP1 gene), hyperlipoproteinemia IIB (APOC2 gene), hyperlipoproteinemia type V (APOA5 gene), familial hypertriglyceridemia (FHTR: familial Hypertryglyceridemia) (APOA5 gene) combined lipase deficiency (CLD: combined lipase deficiency) (LMF1 gene), or hyperlipidemia (LPL gene).

The APOA5 (apolipoprotein AV) gene, located on the long arm of chromosome 11 (11q23), encoding an apolipoprotein involved in regulation of plasma triglyceride. This apolipoprotein is a component of high density lipoproteins. Mutations in this gene have been linked to the hypertriglyceridemia and hyperlipoproteinemia type 5 (HLPP5: Hyperlipoproteinemia 5), familial hypertriglyceridemia (FHTR: Familial Hypertryglyceridemia), a alternacies in chylomicrons are higher, the very low-density lipoprotein (VLDL) and they are decreased low density lipoprotein (/ LDL) and high density (HDL).

The gene APOC2 (Apolipoprotein C-II), located on the long arm of chromosome 19 (19q13.2), encodes a binding protein lipids belonging to the family of genes of apolipoproteins. The protein appears in plasma which is one of the very low-density lipoprotein (VLDL). This protein activates lipoprotein lipase enzyme that hydrolyzes triglycerides and free fatty acids thus provides for Lasa cells. Mutations in this gene cause hyperlipoproteinaemia IIB type, characterized by hypertriglyceridaemia, xatomas and increased risk of pancreatitis and early atherosclerosis. In normolipidemic individuals it is between HDL, while in hipetrigliceridémicos individuals, it is preferably in VLDL and LDL. 1B (HLPP1B: Hyperlipoproteinemia 1B) hyperlipoproteinemia is characterized by autosomal recessive hypertriglyceridemia, xanthomas and increased risk of pancreatitis and early atherosclerosis due to mutations in this gene.

The LIAS gene (Lipoic acid synthetase), located on the short arm of chromosome 4 (4p14), encodes a protein belonging to the family of biotin synthetase and lipoic acid. This protein is localized in mitochondria and plays an important role in the synthesis of alpha - (+) - lipoic acid. Also it participates in the addition of two sulfur atoms in positions C-6 and C-8 in the lipoyl domains lipoate dependent enzymes in the biosynthesis of lipoate converting octanoilados domains in lipoilados derivatives. Piruvatodeshidrogenasa deficiency lipoic acid synthetase (PDHLD: Pyruvate dehydrogenase deficiency lipoic acid synthetase) is an autosomal recessive disorder of mitochondrial metabolism, characterized by early onset of lactic acidosis, deep encephalomyopathy, and pyruvate oxidation defect. Affected individuals have neonatal onset epilepsy, poor growth, psychomotor retardation, muscular hypotonia, lactic acidosis, and elevated concentrations of glycine in blood and urine.

The LMF1 gene (Lipase Maturation Factor 1), located on the short arm of chromosome 16 (16p13.3), encoding a protein found in the endoplasmic reticulum and is involved in the maturation and transport of lipoprotein lipase (LPL) through secretory pathway. Mutations in this gene are associated with the combined lipase deficiency (CLD: Combined Lipase Deficiency). This process is characterized by repeated episodes of pancreatitis, tuberous xanthomas and lipodystrophy, and are caused by deficiency of LPL and hepatic lipase triglyceride (HTGL: Hepatic Triglyceride Lipase).

The GPIHBP1 gene (Glycosylphosphatidyllinositol anchored High Densisity Lipoprotein Binding Protein 1), located on the long arm of chromosome 8 (8q24.3), encoding a protein of capillary endothelial cells that facilitates the processing of triglyceride - rich lipoproteins. The encoded protein is a glycosylphosphatidylinositol, which acts as a carrier of lipoprotein lipase (LPL) from the capillary lumen to the subendothelial space. Its mutations cause hyperlipoproteinemia type 1D (HLPP1D: Hyperlipoproteinemia 1D), an autosomal recessive disorder characterized by hyperlipoproteinemia, diminished concentrations of LPL, high triglyceride levels, and refractory to the diet chylomicronemia.

The LPL gene (lipoprotein lipase), located on the short arm of chromosome 8 (8p22), encodes the enzyme lipoprotein lipase, which is mainly found on the surface of endothelial cells of the capillaries in the muscles and adipose tissue. Lipoprotein lipase plays an important break fats as triglycerides paper, which are transported from various organs into the blood by lipoproteins. This lipoprotein lipase cleaves triglycerides transported by two different types of lipoproteins, fats leading to blood from different organs. Gut fat, ingested by diet, they are transported to the blood by lipoproteins called chylomicrons. The very low-density lipoprotein (VLDL carry triglycerides from the liver into the bloodstream. When lipoprotein lipase cleaves triglycerides, fat molecules are used to provide power, or are stored in tissues. Mutations in this gene cause Familial lipoprotein lipase deficiency. mutated variants of lipoprotein lipase are enzymes with altered to cleave triglycerides capacity. in some instances, the enzyme is overactive resulting in low levels of fat. in other cases decreases its activity leading to a rise of the fat levels, hyperlipidemia. individuals with hyperlipidemia have higher risk of developing arteriosclerosis, with the risk of trigger a heart attack, stroke stroke.  

Tests in IVAMI: in IVAMI perform detection of mutations associated with hypertriglyceridemia, by complete PCR amplification of the exons of APOA5, APOC2, LIPI LMF1, GPIHBP1 and LPL genes, respectively, and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).