Details of Disease

General Information of Disease (ID: DISL1CE3)

• Disease Name: Hyperlipidemia, familial combined, LPL related
• Synonyms: hyperlipidemia, familial combined; familial combined hyperlipidemia; FCHL; combined hyperlipidemia, familial
• Definition: Editor note: the OMIM:144250 entry refers to the LPL-caused form
• Disease Hierarchy:
  DIS4R2OG: Hyperlipidaemia
  DISL1CE3: Hyperlipidemia, familial combined, LPL related
• Disease Identifiers:
  MONDO ID: MONDO_0007759
  MESH ID: D006950
  UMLS CUI: C0020474
  OMIM ID: 144250
  MedGen ID: 6965
  HPO ID: HP:0008158
  SNOMED CT ID: 238040008

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 10 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Atorvastatin	DMF28YC	Approved	Small molecular drug	[1]
Ezetimibe	DM7A8TW	Approved	Small molecular drug	[2]
Fenofibrate	DMFKXDY	Approved	Small molecular drug	[3]
Fluvastatin	DM4MDJY	Approved	Small molecular drug	[4]
Lovastatin	DM9OZWQ	Approved	Small molecular drug	[5]
Pitavastatin	DMJH792	Approved	NA	[6]
Pravastatin	DM6A0X7	Approved	Small molecular drug	[7]
Rosuvastatin	DMMIQ7G	Approved	Small molecular drug	[8]
Simvastatin	DM30SGU	Approved	Small molecular drug	[9]
Vitamin B3	DMQVRZH	Approved	Small molecular drug	[10]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 9 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
C3	TTJGY7A	Limited	Biomarker	[11]
LPA	TTU9LGY	Limited	Biomarker	[12]
APOA4	TTNC3WS	Strong	Genetic Variation	[13]
APOC3	TTXOZQ1	Strong	Biomarker	[14]
FABP2	TTS4YLO	Strong	Genetic Variation	[15]
FASLG	TTO7014	Strong	Biomarker	[16]
LPL	TTOF3WZ	Strong	Autosomal dominant	[17]
LPL	TTOF3WZ	Strong	Genetic Variation	[18]
RXRG	TTH029C	Strong	Biomarker	[19]

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
CYP7A1	DEDZRQ1	Strong	Genetic Variation	[20]

This Disease Is Related to 16 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ADD1	OTTF68DC	Strong	Genetic Variation	[21]
APOA5	OTEVKLVA	Strong	Genetic Variation	[22]
ATAD1	OTJ02XFL	Strong	Biomarker	[23]
C5AR2	OTP1Q82J	Strong	Genetic Variation	[24]
DLX4	OTLWVCN4	Strong	Biomarker	[25]
FADS3	OT9RVXGE	Strong	Genetic Variation	[26]
JPH3	OTHTJO2I	Strong	Genetic Variation	[27]
LIPC	OTZY5SC9	Strong	Genetic Variation	[28]
LPL	OTTW0267	Strong	Autosomal dominant	[17]
LYPLA2	OT03UIYC	Strong	Altered Expression	[29]
MLXIPL	OTR9MLLW	Strong	Genetic Variation	[20]
OSBP	OT7R0OQQ	Strong	Genetic Variation	[30]
OSBPL10	OT0TFMBE	Strong	Genetic Variation	[30]
OSBPL9	OTY7IG2V	Strong	Genetic Variation	[30]
PCDH15	OTU9C2EH	Strong	Genetic Variation	[31]
TGIF1	OTN9VHAG	Strong	Biomarker	[32]

References

• [1] Atorvastatin FDA Label
• [2] Ezetimibe FDA Label
• [3] Fenofibrate FDA Label
• [4] Fluvastatin FDA Label
• [5] Lovastatin FDA Label
• [6] Pitavastatin FDA Label
• [7] Pravastatin FDA Label
• [8] Rosuvastatin FDA Label
• [9] Simvastatin FDA Label
• [10] A standard database for drug repositioning. Sci Data. 2017 Mar 14;4:170029.
• [11] Delayed and exaggerated postprandial complement component 3 response in familial combined hyperlipidemia.Arterioscler Thromb Vasc Biol. 2002 May 1;22(5):811-6. doi: 10.1161/01.atv.0000014079.98335.72.
• [12] A novel mutation of the apolipoprotein A-I gene in a family with familial combined hyperlipidemia.Atherosclerosis. 2008 May;198(1):145-51. doi: 10.1016/j.atherosclerosis.2007.09.017. Epub 2007 Oct 24.
• [13] Two novel apolipoprotein A-IV variants in individuals with familial combined hyperlipidemia and diminished levels of lipoprotein lipase activity.Hum Mutat. 1996;8(4):319-25. doi: 10.1002/(SICI)1098-1004(1996)8:4<319::AID-HUMU4>3.0.CO;2-2.
• [14] Identification of the PPARA locus on chromosome 22q13.3 as a modifier gene in familial combined hyperlipidemia.Mol Genet Metab. 2002 Dec;77(4):274-81. doi: 10.1016/s1096-7192(02)00174-9.
• [15] Common variants in the lipoprotein lipase gene, but not those in the insulin receptor substrate-1, the beta3-adrenergic receptor, and the intestinal fatty acid binding protein-2 genes, influence the lipid phenotypic expression in familial combined hyperlipidemia.Metabolism. 2002 Oct;51(10):1298-305. doi: 10.1053/meta.2002.35197.
• [16] Decreased circulating Fas ligand in patients with familial combined hyperlipidemia or carotid atherosclerosis: normalization by atorvastatin. J Am Coll Cardiol. 2004 Apr 7;43(7):1188-94. doi: 10.1016/j.jacc.2003.10.046.
• [17] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [18] A novel variant in LPL gene is associated with familial combined hyperlipidemia.Biofactors. 2020 Jan;46(1):94-99. doi: 10.1002/biof.1570. Epub 2019 Oct 10.
• [19] High frequency of a retinoid X receptor gamma gene variant in familial combined hyperlipidemia that associates with atherogenic dyslipidemia.Arterioscler Thromb Vasc Biol. 2007 Apr;27(4):923-8. doi: 10.1161/01.ATV.0000258945.76141.8a. Epub 2007 Feb 1.
• [20] Common genetic variants contribute to primary hypertriglyceridemia without differences between familial combined hyperlipidemia and isolated hypertriglyceridemia.Circ Cardiovasc Genet. 2014 Dec;7(6):814-21. doi: 10.1161/CIRCGENETICS.114.000522. Epub 2014 Aug 30.
• [21] Association between the alpha-adducin Gly460Trp polymorphism and systolic blood pressure in familial combined hyperlipidemia.Am J Hypertens. 2001 Dec;14(12):1185-90. doi: 10.1016/s0895-7061(01)02216-6.
• [22] Association of USF1 and APOA5 polymorphisms with familial combined hyperlipidemia in an Italian population.Mol Cell Probes. 2015 Feb;29(1):19-24. doi: 10.1016/j.mcp.2014.10.002. Epub 2014 Oct 13.
• [23] Apolipoprotein B-100 Hopkins (arginine4019----tryptophan). A new apolipoprotein B-100 variant in a family with premature atherosclerosis and hyperapobetalipoproteinemia.JAMA. 1989 Oct 13;262(14):1980-8. doi: 10.1001/jama.262.14.1980.
• [24] S323I polymorphism of the C5L2 gene was not identified in a Chinese population with familial combined hyperlipidemia or with type 2 diabetes.Genet Mol Res. 2011 Dec 22;10(4):3256-66. doi: 10.4238/2011.December.22.4.
• [25] Further insights into the pathophysiology of hyperapobetalipoproteinemia: role of basic proteins I, II, III.Clin Chem. 1991 Mar;37(3):317-26.
• [26] A systems genetics approach implicates USF1, FADS3, and other causal candidate genes for familial combined hyperlipidemia.PLoS Genet. 2009 Sep;5(9):e1000642. doi: 10.1371/journal.pgen.1000642. Epub 2009 Sep 11.
• [27] An omega-3 polyunsaturated fatty acid concentrate increases plasma high-density lipoprotein 2 cholesterol and paraoxonase levels in patients with familial combined hyperlipidemia.Metabolism. 2004 Feb;53(2):153-8. doi: 10.1016/j.metabol.2003.09.007.
• [28] The V73M mutation in the hepatic lipase gene is associated with elevated cholesterol levels in four Dutch pedigrees with familial combined hyperlipidemia.Atherosclerosis. 2000 Aug;151(2):443-50. doi: 10.1016/s0021-9150(99)00428-1.
• [29] Differential gene expression of blood-derived cell lines in familial combined hyperlipidemia.Arterioscler Thromb Vasc Biol. 2004 Nov;24(11):2149-54. doi: 10.1161/01.ATV.0000145978.70872.63. Epub 2004 Sep 23.
• [30] OSBPL10, a novel candidate gene for high triglyceride trait in dyslipidemic Finnish subjects, regulates cellular lipid metabolism.J Mol Med (Berl). 2009 Aug;87(8):825-35. doi: 10.1007/s00109-009-0490-z. Epub 2009 Jun 25.
• [31] A nonsynonymous SNP within PCDH15 is associated with lipid traits in familial combined hyperlipidemia.Hum Genet. 2010 Jan;127(1):83-9. doi: 10.1007/s00439-009-0749-z. Epub 2009 Oct 9.
• [32] Pathway analysis detect potential mechanism for familial combined hyperlipidemia.Eur Rev Med Pharmacol Sci. 2013 Jul;17(14):1909-15.