Functional analysis of four LDLR 5′UTR and promoter variants in patients with familial hypercholesterolaemia

European Journal of Human Genetics

Volumn 23, Issue 6, 2015, Pages 790-795

  Khamis, Amna ^a   Palmen, Jutta ^a   Lench, Nick ^b   Taylor, Alison ^b   Badmus, Ebele ^a   Leigh, Sarah ^a   Humphries, Steve E ^a  

^a ROYAL FREE AND UNIVERSITY COLLEGE MEDICAL SCHOOL   (United Kingdom)

^b GREAT ORMOND STREET HOSPITAL   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

LOW DENSITY LIPOPROTEIN RECEPTOR; LUCIFERASE; NUCLEAR PROTEIN; STEROL REGULATORY ELEMENT BINDING PROTEIN 1; STEROL REGULATORY ELEMENT BINDING PROTEIN 2; 5' UNTRANSLATED REGION; LDLR PROTEIN, HUMAN;

5' UNTRANSLATED REGION; ALLELE; ARTICLE; COMPUTER MODEL; ENZYME ACTIVITY; FAMILIAL HYPERCHOLESTEROLEMIA; GEL MOBILITY SHIFT ASSAY; GENE EXPRESSION; GENE FUNCTION; GENETIC VARIABILITY; HUMAN; IN VITRO STUDY; LUCIFERASE ASSAY; PREDICTION; PRIORITY JOURNAL; PROMOTER REGION; GENETICS; HYPERCHOLESTEROLEMIA; METABOLISM; MOLECULAR GENETICS; NUCLEOTIDE SEQUENCE; SINGLE NUCLEOTIDE POLYMORPHISM; TUMOR CELL LINE;

5' UNTRANSLATED REGIONS; BASE SEQUENCE; CELL LINE, TUMOR; HUMANS; HYPERCHOLESTEROLEMIA; MOLECULAR SEQUENCE DATA; POLYMORPHISM, SINGLE NUCLEOTIDE; PROMOTER REGIONS, GENETIC; RECEPTORS, LDL;

EID: 84929266164     PISSN: 10184813     EISSN: 14765438     Source Type: Journal    
DOI: 10.1038/ejhg.2014.199     Document Type: Article

References (35)

1. Marks D, Thorogood M, Neil HA, Humphries SE: A review on the diagnosis, natural history, and treatment of familial hypercholesterolaemia. Atherosclerosis 2003; 168: 1-14.
2. Nordestgaard BG, Chapman MJ, Humphries SE et al: Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society. Eur Heart J 2013; 34: 3478-90a.
3. Soutar AK, Naoumova RP: Mechanisms of disease: genetic causes of familial hypercholesterolemia. Nature clinical practice. Cardiovasc Med 2007; 4: 214-225.
4. Varret M, Abifadel M, Rabes JP, Boileau C: Genetic heterogeneity of autosomal dominant hypercholesterolemia. Clin Genet 2008; 73: 1-13.
5. Leigh SE, Foster AH, Whittall RA, Hubbart CS, Humphries SE: Update and analysis of the University College London low density lipoprotein receptor familial hypercholesterolemia database. Ann Hum Genet 2008; 72 (Pt 4): 485-498.
6. Usifo E, Leigh SE, Whittall RA et al: Low-density lipoprotein receptor gene familial hypercholesterolemia variant database: update and pathological assessment. Ann Hum Genet 2012; 76: 387-401.
7. Liu J, Ahlborn TE, Briggs MR, Kraemer FB: Identification of a novel sterol-independent regulatory element in the human low density lipoprotein receptor promoter. J Biol Chem 2000; 275: 5214-5221.
8. Smith AJ, Ahmed F, Nair D et al: A functional mutation in the LDLR promoter (-139C4G) in a patient with familial hypercholesterolemia. Eur J Hum Genet 2007; 15: 1186-1189.
9. Natesampillai S, Fernandez-Zapico ME, Urrutia R, Veldhuis JD: A novel functional interaction between the Sp1-like protein KLF13 and SREBP-Sp1 activation complex underlies regulation of low density lipoprotein receptor promoter function. J Biol Chem 2006; 281: 3040-3047.
10. Francova H, Trbusek M, Zapletalova P, Kuhrova V: New promoter mutations in the low-density lipoprotein receptor gene which induce familial hypercholesterolaemia phenotype: molecular and functional analysis. J Inherit Metab Dis 2004; 27: 523-528.
11. Medeiros AM, Alves AC, Francisco V, Bourbon M: Update of the Portuguese Familial Hypercholesterolaemia Study. Atherosclerosis 2010; 212: 553-558.
12. Taylor A, Wang D, Patel K et al: Mutation detection rate and spectrum in familial hypercholesterolaemia patients in the UK pilot cascade project. Clin Genet 2010; 77: 572-580.
13. Cartharius K, Frech K, Grote K et al: MatInspector and beyond: promoter analysis based on transcription factor binding sites. Bioinformatics 2005; 21: 2933-2942.
14. Kel AE, Gossling E, Reuter I, Cheremushkin E, Kel-Margoulis OV, Wingender E: MATCH: A tool for searching transcription factor binding sites in DNA sequences. Nucleic Acids Res 2003; 31: 3576-3579.
15. De Castro-Oros I, Pampin S, Bolado-Carrancio A et al: Functional analysis of LDLR promoter and 5' UTR mutations in subjects with clinical diagnosis of familial hypercholesterolemia. Hum Mutat 2011; 32: 868-872.
16. Yang WS, Nevin DN, Peng R, Brunzell JD, Deeb SS: A mutation in the promoter of the lipoprotein lipase (LPL) gene in a patient with familial combined hyperlipidemia and low LPL activity. Proc Natl Acad Sci USA 1995; 92: 4462-4466.
17. Nakshatri H, Nakshatri P, Currie RA: Interaction of Oct-1 with TFIIB. Implications for a novel response elicited through the proximal octamer site of the lipoprotein lipase promoter. J Biol Chem 1995; 270: 19613-19623.
18. Li H, Dong B, Park SW, Lee HS, Chen W, Liu J: Hepatocyte nuclear factor 1alpha plays a critical role in PCSK9 gene transcription and regulation by the natural hypocholesterolemic compound berberine. J Biol Chem 2009; 284: 28885-28895.
19. Dhawan P, Chang R, Mehta KD: Identification of essential nucleotides of the FP1 element responsible for enhancement of low density lipoprotein receptor gene transcription. Nucleic Acids Res 1997; 25: 4132-4138.
20. Scholtz CL, Peeters AV, Hoogendijk CF et al: Mutation-59c-4t in repeat 2 of the LDL receptor promoter: reduction in transcriptional activity and possible allelic interaction in a South African family with familial hypercholesterolaemia. Hum Mol Genet 1999; 8: 2025-2030.
21. Bodamer OA, Bercovich D, Schlabach M, Ballantyne C, Zoch D, Beaudet AL: Use of denaturing HPLC to provide efficient detection of mutations causing familial hypercholesterolemia. Clin Chem 2002; 48: 1913-1918.
22. Lind S, Rystedt E, Eriksson M, Wiklund O, Angelin B, Eggertsen G: Genetic characterization of Swedish patients with familial hypercholesterolemia: A heterogeneous pattern of mutations in the LDL receptor gene. Atherosclerosis 2002; 163: 399-407.
23. Fouchier SW, Kastelein JJ, Defesche JC: Update of the molecular basis of familial hypercholesterolemia in The Netherlands. Hum Mutat 2005; 26: 550-556.
24. Peeters AV, Kotze MJ, Scholtz CL et al: A 3-basepair deletion in repeat 1 of the LDL receptor promoter reduces transcriptional activity in a South African Pedi. J Lipid Res 1998; 39: 1021-1024.
25. Dedoussis GV, Genschel J, Bochow B et al: Molecular characterization of familial hypercholesterolemia in German and Greek patients. Hum Mutat 2004; 23: 285-286.
26. Francova H, Trbusek M, Zapletalova P, Kuhrova V: New promoter mutations in the lowdensity lipoprotein receptor gene which induce familial hypercholesterolaemia phenotype: molecular and functional analysis. J Inherit Metab Dis 2004; 27: 523-528.
27. Day IN, Whittall RA, O'Dell SD et al: Spectrum of LDL receptor gene mutations in heterozygous familial hypercholesterolemia. Hum Mutat 1997; 10: 116-127.
28. Mozas P, Galetto R, Albajar M, Ros E, Pocovi M, Rodriguez-Rey JC: A mutation (-49C4T) in the promoter of the low density lipoprotein receptor gene associated with familial hypercholesterolemia. J Lipid Res 2002; 43: 13-18.
29. Dedoussis GV, Pitsavos C, Kelberman D et al: FH-Pyrgos: A novel mutation in the promoter (-45delT) of the low-density lipoprotein receptor gene associated with familial hypercholesterolemia. Clin Genet 2003; 64: 414-419.
30. Sun XM, Neuwirth C, Wade DP, Knight BL, Soutar AK: A mutation (T-45C) in the promoter region of the low-density-lipoprotein (LDL)-receptor gene is associated with a mild clinical phenotype in a patient with heterozygous familial hypercholesterolaemia (FH). Hum Mol Genet 1995; 4: 2125-2129.
31. Hobbs HH, Brown MS, Goldstein JL: Molecular genetics of the LDL receptor gene in familial hypercholesterolemia. Hum Mutat 1992; 1: 445-466.
32. Koivisto UM, Palvimo JJ, Janne OA, Kontula K: A single-base substitution in the proximal Sp1 site of the human low density lipoprotein receptor promoter as a cause of heterozygous familial hypercholesterolemia. Proc Natl Acad Sci USA 1994; 91: 10526-10530.
33. Laurie AD, Scott RS, George PM: Genetic screening of patients with familial hypercholesterolaemia (FH): A New Zealand perspective. Atheroscler Suppl 2004; 5: 13-15.
34. Mozas P, Castillo S, Tejedor D et al: Molecular characterization of familial hypercholesterolemia in Spain: identification of 39 novel and 77 recurrent mutations in LDLR. Hum Mutat 2004; 24: 187.
35. Sozen MM, Whittall R, Oner C et al: The molecular basis of familial hypercholesterolaemia in Turkish patients. Atherosclerosis 2005; 180: 63-71.