LIPID inCode® is a genetic test for the diagnosis of Familial Hypercholesterolemia (FH) with further coronary risk stratification of the patient.
Genetic testing for FH is the only definitive method of confirming the disease. Confirmation of FH in a patient makes it possible to analyse at-risk relatives and identify other previously undetected affected individuals.
LIPID inCode® assesses the probability of Polygenic Hypercholesterolemia, another source of primary hypercholesterolemia, as well as the genetic coronary risk thanks to the CARDIO inCode® Polygenic Score. Both are independent coronary risk factors. In addition, the test provides useful information for clinical and therapeutic management of the patient: pharmacogenetics of statins and predisposition to elevated Lp(a) levels.
LIPID inCode® offers advanced assessment of hypercholesterolemia and other cardiovascular risk factors to optimise prevention strategies and avoid coronary events.
Genes/variants analysed and technology
The test analyses six genes commonly involved in Familial Hypercholesterolemia (FH) using next-generation sequencing technology. This includes the LDLR, APOB, PCSK9 and APOE genes associated with autosomal dominant Familial Hypercholesterolemia, the LDLRAP1 gene associated with Autosomal Recessive Hypercholesterolemia (ARH) and the LIPA gene associated with Lysosomal Acid Lipase Deficiency (LALD).
The promoter and coding regions of each gene, including exon-intron boundaries,are analysed, in addition to copy number variations (CNV’s), such as deletions/duplications in the LDLR gene. CNV’ss are confirmed by Multiplex Ligation-dependent Probe Amplification (MLPA), and other selected variants by Sanger sequencing. In addition, the test detects the presence or absence of 28 common genetic variants known as Single Nucleotide Polymorphisms (SNPs), related to Polygenic Hypercholesterolemia, cardiovascular risk, and pharmacogenetics.
By genotyping these carefully selected SNPs, information can be gained that is useful in clinical and therapeutic management of patients. If a germline pathogenic/likely pathogenic variant is identified by LIPID inCode® testing, this confirms a genetic diagnosis of Familial Hypercholesterolemia in the individual, and genetic testing for the presence of this variant only is available to in at-risk family members using Sanger sequencing technology and MLPA.
- Patients with symptoms of FH.
- Patients with resistant or uncontrolled hypercholesterolemia.
- Patients with myocardial infarction and other atherosclerotic cardiovascular diseases at young ages (men <55 years and women <60 years)
- Relatives of patients with FH and positive genetic studies (familial cascade screening).
LIPID inCode® is aligned with the recommendations of the FH expert panel of the Journal of the American College of Cardiology (JACC 2018). In addition, the test provides information on the clinical impact and genotype-phenotype correlation of detected variants (epidemiological data from the SAFEHEART registry, with follow-up of more than 5,000 patients with a genetic diagnosis of HF, and its own registry of described genetic variants, with information on more than 2,200 variants).
Polygenic Hypercholesterolemia is evaluated by the Futema et al. validated Genetic Risk Score (LDL-C Score).
The CARDIO inCode® Polygenic Score has been validated in more than 75,000 patients of different ethnicities and evaluates the coronary genetic load, an independent risk factor from classical CV risk factors that weights around 50% in the risk of developing a coronary event.
Numerous scientific articles published in prestigious national and international journals have been written about LIPID inCode®:
- Arrobas Velilla T, Brea A and Valdivielso P. Implementation of a biochemical, clinical, and genetic screening programme for familial hypercholesterolemia in 26 centres in Spain: The ARIAN study. Frontiers in Genetics 2022;13:971651. Doi:10.3389/fgene.2022.971651
- Omlastroni E et al. Twelve Variants Polygenic Score for Low-DensityLipoprotein Cholesterol Distribution in a Large Cohort of Patients With Clinically Diagnosed Familial Hypercholesterolemia With or Without Causative Mutations. J Am Heart Assoc. 2022;11:e023668. DOI: 10.1161/JAHA.121.023668
- Sabatel-Pérez, F. et al. Improving Familial Hypercholesterolemia Index Case Detection: Sequential Active Screening from Centralized Analytical Data. J. Clin. Med. 2021;10:749
- Gutiérrez-Cortizo EN, Romero-Jiménez MJ, Mansilla Rodríguez ME et al. Detección de hipercolesterolemia familiar a través de datos analíticos centralizados. Programa DETECTA HF HUELVA. Endocrinología, Diabetes y Nutrición 2021;68(7):450-457
- Roa Garrido J et al. Particularidades genéticas y bioquímicas de la hipercolesterolemia familiar en el suroeste de la Península Ibérica. Clínica e Investigación en Arteriosclerosis 2021;33:62-69
- Amor-Salamanca A et al. Genetically confirmed familial hypercholesterolemia in patients with acute coronary syndrome. J Am Coll Cardiol 2017;70:1732-40
- Sturm AC et al. Clinical genetic testing for familial hypercholesterolemia. JACC Scientific Expert Panel. JACC 2018;72(6):662-680
References in the text:
- Sturm AC et al. Clinical Genetic Testing for Familial Hypercholesterolemia. JACC Scientific Expert Panel. JACC 2018;72(6):662-80
- Futema M et al.Clinical utility of the polygenic LDL-C SNP score in familial hypercholesterolemia. Atherosclerosis 2018;277:457-463