NPC1L1: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
m (→‎top: task, replaced: J. Clin. Invest → J. Clin. Invest. using AWB)
 
imported>Boghog
m (typo)
 
Line 1: Line 1:
{{infobox protein
{{infobox gene}}
|Name=NPC1 (Niemann-Pick disease, type C1, gene)-like 1
'''Niemann-Pick C1-Like 1''' (NPC1L1) is a gene associated with NPC1, mutation of which results in [[Niemann-Pick disease]]. It codes for Niemann-Pick C1-like protein 1, found on the [[gastrointestinal tract]] [[epithelial]] cells<ref name="Garcia-Calvo2005">{{cite journal | vauthors = Garcia-Calvo M, Lisnock J, Bull HG, Hawes BE, Burnett DA, Braun MP, Crona JH, Davis HR, Dean DC, Detmers PA, Graziano MP, Hughes M, Macintyre DE, Ogawa A, O'neill KA, Iyer SP, Shevell DE, Smith MM, Tang YS, Makarewicz AM, Ujjainwalla F, Altmann SW, Chapman KT, Thornberry NA | display-authors = 6 | title = The target of ezetimibe is Niemann-Pick C1-Like 1 (NPC1L1) | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 102 | issue = 23 | pages = 8132–7 | date = June 2005 | pmid = 15928087 | pmc = 1149415 | doi = 10.1073/pnas.0500269102 }}</ref> as well as in [[hepatocytes]].<ref name="Temel">{{cite journal | vauthors = Temel RE, Tang W, Ma Y, Rudel LL, Willingham MC, Ioannou YA, Davies JP, Nilsson LM, Yu L | title = Hepatic Niemann-Pick C1-like 1 regulates biliary cholesterol concentration and is a target of ezetimibe | journal = The Journal of Clinical Investigation | volume = 117 | issue = 7 | pages = 1968–78 | date = July 2007 | pmid = 17571164 | pmc = 1888567 | doi = 10.1172/JCI30060 }}</ref>  Specifically, it appears to bind to a critical mediator of cholesterol absorption.
|caption=
|image=
|width=
|HGNCid=7898
|Symbol=NPC1L1
|AltSymbols=
|EntrezGene=29881
|OMIM=608010
|RefSeq=NM_013389
|UniProt=Q9UHC9
|PDB=
|ECnumber=
|Chromosome=7
|Arm=p
|Band=13
|LocusSupplementaryData=
}}
'''Niemann-Pick C1-Like 1''' (NPC1L1) is a gene associated with NPC1 which mutation results in [[Niemann-Pick disease]]. It codes for Niemann-Pick C1-like protein 1, found on the [[gastrointestinal tract]] [[epithelial]] cells<ref name="Garcia-Calvo2005">{{cite journal | last1 = Garcia-Calvo | first1 = M | last2 = Lisnock | first2 = J | last3 = Bull | first3 = HG | last4 = Hawes | first4 = BE | last5 = Burnett | first5 = DA | last6 = Braun | first6 = MP | display-authors = 6 | last7 = et al | year = 2005 | title = The target of ezetimibe is Niemann-Pick C1-Like 1 (NPC1L1) | journal = [[Proceedings of the National Academy of Sciences of the United States of America|Proc Natl Acad Sci U S A]] | volume = 102 | issue = 23| pages = 8132–7 | doi = 10.1073/pnas.0500269102 | pmid = 15928087 | pmc=1149415}}</ref> as well as in [[hepatocytes]].<ref name="Temel">{{cite journal | last1 = Temel | first1 = Ryan E. | last2 = Tang | first2 = Weiqing | last3 = Ma | first3 = Yinyan | last4 = Rudel | first4 = Lawrence L. | last5 = Willingham | first5 = Mark C. | last6 = Ioannou | first6 = Yiannis A. | last7 = Davies | first7 = Joanna P. | last8 = Nilsson | first8 = Lisa-Mari | last9 = Yu | first9 = Liqing | year = 2007 | title = Hepatic Niemann-Pick C1-like 1 regulates biliary cholesterol concentration and is a target of ezetimibe | url = | journal = J. Clin. Invest. | volume = | issue = | page = }}</ref>  Specifically, it appears to bind to a critical mediator of cholesterol absorption.


The drug [[ezetimibe]] blocks the NPC1L1 causing a reduction in cholesterol absorption, resulting in a blood cholesterol reduction of between 15-20%. Polymorphic variations in NPC1L1 gene could be associated with non-response to ezetimibe treatment.<ref>Niemann-Pick C1-like protein 1 precursor - Homo sapiens (Human). Available from: http://www.uniprot.org/uniprot/Q9UHC9 Accessed 3 September 2012</ref>
The drug [[ezetimibe]] blocks NPC1L1 causing a reduction in cholesterol absorption, resulting in a blood cholesterol reduction of between 15-20%.<ref name="pmid17587760">{{cite journal | vauthors = Davis HR, Veltri EP | title = Zetia: inhibition of Niemann-Pick C1 Like 1 (NPC1L1) to reduce intestinal cholesterol absorption and treat hyperlipidemia | journal = Journal of Atherosclerosis and Thrombosis | volume = 14 | issue = 3 | pages = 99–108 | date = June 2007 | pmid = 17587760 | doi = 10.5551/jat.14.99 }}</ref> Polymorphic variations in NPC1L1 gene could be associated with non-response to ezetimibe treatment.<ref>{{UniProt Full|Q9UHC9|Niemann-Pick C1-like protein 1 precursor - Homo sapiens (Human)}}</ref>


NPC1L1 has been shown to be an accessory receptor for [[Hepatitis C virus]] entry into cells, and thus [[ezetimibe]] might be used as a therapeutic strategy<ref>{{cite journal|last1=Sainz|first1=Bruno|last2=Barretto|first2=Naina|last3=Martin|first3=Danyelle N|last4=Hiraga|first4=Nobuhiko|last5=Imamura|first5=Michio|last6=Hussain|first6=Snawar|last7=Marsh|first7=Katherine A|last8=Yu|first8=Xuemei|last9=Chayama|first9=Kazuaki|last10=Alrefai|first10=Waddah A|last11=Uprichard|first11=Susan L|title=Identification of the Niemann-Pick C1–like 1 cholesterol absorption receptor as a new hepatitis C virus entry factor|journal=Nature Medicine|date=8 January 2012|volume=18|issue=2|pages=281–285|doi=10.1038/nm.2581|pmid=22231557|pmc=3530957}}</ref>
NPC1L1 has been shown to be an accessory receptor for [[hepatitis C virus]] entry into cells, and thus [[ezetimibe]] might be used as a therapeutic strategy.<ref>{{cite journal | vauthors = Sainz B, Barretto N, Martin DN, Hiraga N, Imamura M, Hussain S, Marsh KA, Yu X, Chayama K, Alrefai WA, Uprichard SL | title = Identification of the Niemann-Pick C1-like 1 cholesterol absorption receptor as a new hepatitis C virus entry factor | journal = Nature Medicine | volume = 18 | issue = 2 | pages = 281–5 | date = January 2012 | pmid = 22231557 | pmc = 3530957 | doi = 10.1038/nm.2581 }}</ref>


==See also==
As cancer appeared more frequently in patients treated with [[simvastatin]]-[[ezetimibe]] combination therapy in one clinical trial,<ref name="pmid18765433">{{cite journal | vauthors = Rossebø AB, Pedersen TR, Boman K, Brudi P, Chambers JB, Egstrup K, Gerdts E, Gohlke-Bärwolf C, Holme I, Kesäniemi YA, Malbecq W, Nienaber CA, Ray S, Skjaerpe T, Wachtell K, Willenheimer R | display-authors = 6 | collaboration = SEAS Investigators | title = Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis | journal = The New England Journal of Medicine | volume = 359 | issue = 13 | pages = 1343–56 | date = September 2008 | pmid = 18765433 | doi = 10.1056/NEJMoa0804602 }}</ref> it had been hypothesized that NPC1L1 by ezetimibe might be associated with an increase cancer risk.<ref name="pmid18765432">{{cite journal | vauthors = Peto R, Emberson J, Landray M, Baigent C, Collins R, Clare R, Califf R | title = Analyses of cancer data from three ezetimibe trials | journal = The New England Journal of Medicine | volume = 359 | issue = 13 | pages = 1357–66 | date = September 2008 | pmid = 18765432 | doi = 10.1056/NEJMsa0806603 }}</ref>  However a meta-analysis of ezetimibe clinical data showed no increased risk of cancer from treatment with ezetimibe.<ref name="pmid26301648">{{cite journal | vauthors = Savarese G, De Ferrari GM, Rosano GM, Perrone-Filardi P | title = Safety and efficacy of ezetimibe: A meta-analysis | journal = International Journal of Cardiology | volume = 201 | issue = | pages = 247–52 | date = December 2015 | pmid = 26301648 | doi = 10.1016/j.ijcard.2015.08.103 | url = }}</ref>
 
== See also ==
* [[Ezetimibe]]
* [[Ezetimibe]]


==External links==
== External links ==
{{commons category}}
{{commons category}}
* {{MeshName|NPC1L1+protein,+human}}
* {{MeshName|NPC1L1+protein,+human}}


==References==
== References ==
{{Reflist}}
{{Reflist}}


{{biochem-stub}}
{{biochem-stub}}

Latest revision as of 04:33, 23 November 2018

VALUE_ERROR (nil)
Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

n/a

n/a

Ensembl

n/a

n/a

UniProt

n/a

n/a

RefSeq (mRNA)

n/a

n/a

RefSeq (protein)

n/a

n/a

Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

Niemann-Pick C1-Like 1 (NPC1L1) is a gene associated with NPC1, mutation of which results in Niemann-Pick disease. It codes for Niemann-Pick C1-like protein 1, found on the gastrointestinal tract epithelial cells[1] as well as in hepatocytes.[2] Specifically, it appears to bind to a critical mediator of cholesterol absorption.

The drug ezetimibe blocks NPC1L1 causing a reduction in cholesterol absorption, resulting in a blood cholesterol reduction of between 15-20%.[3] Polymorphic variations in NPC1L1 gene could be associated with non-response to ezetimibe treatment.[4]

NPC1L1 has been shown to be an accessory receptor for hepatitis C virus entry into cells, and thus ezetimibe might be used as a therapeutic strategy.[5]

As cancer appeared more frequently in patients treated with simvastatin-ezetimibe combination therapy in one clinical trial,[6] it had been hypothesized that NPC1L1 by ezetimibe might be associated with an increase cancer risk.[7] However a meta-analysis of ezetimibe clinical data showed no increased risk of cancer from treatment with ezetimibe.[8]

See also

External links

References

  1. ↑ Garcia-Calvo M, Lisnock J, Bull HG, Hawes BE, Burnett DA, Braun MP, et al. (June 2005). "The target of ezetimibe is Niemann-Pick C1-Like 1 (NPC1L1)". Proceedings of the National Academy of Sciences of the United States of America. 102 (23): 8132–7. doi:10.1073/pnas.0500269102. PMC 1149415. PMID 15928087.
  2. ↑ Temel RE, Tang W, Ma Y, Rudel LL, Willingham MC, Ioannou YA, Davies JP, Nilsson LM, Yu L (July 2007). "Hepatic Niemann-Pick C1-like 1 regulates biliary cholesterol concentration and is a target of ezetimibe". The Journal of Clinical Investigation. 117 (7): 1968–78. doi:10.1172/JCI30060. PMC 1888567. PMID 17571164.
  3. ↑ Davis HR, Veltri EP (June 2007). "Zetia: inhibition of Niemann-Pick C1 Like 1 (NPC1L1) to reduce intestinal cholesterol absorption and treat hyperlipidemia". Journal of Atherosclerosis and Thrombosis. 14 (3): 99–108. doi:10.5551/jat.14.99. PMID 17587760.
  4. ↑ Universal protein resource accession number Q9UHC9 for "Niemann-Pick C1-like protein 1 precursor - Homo sapiens (Human)" at UniProt.
  5. ↑ Sainz B, Barretto N, Martin DN, Hiraga N, Imamura M, Hussain S, Marsh KA, Yu X, Chayama K, Alrefai WA, Uprichard SL (January 2012). "Identification of the Niemann-Pick C1-like 1 cholesterol absorption receptor as a new hepatitis C virus entry factor". Nature Medicine. 18 (2): 281–5. doi:10.1038/nm.2581. PMC 3530957. PMID 22231557.
  6. ↑ Rossebø AB, Pedersen TR, Boman K, Brudi P, Chambers JB, Egstrup K, et al. (SEAS Investigators) (September 2008). "Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis". The New England Journal of Medicine. 359 (13): 1343–56. doi:10.1056/NEJMoa0804602. PMID 18765433.
  7. ↑ Peto R, Emberson J, Landray M, Baigent C, Collins R, Clare R, Califf R (September 2008). "Analyses of cancer data from three ezetimibe trials". The New England Journal of Medicine. 359 (13): 1357–66. doi:10.1056/NEJMsa0806603. PMID 18765432.
  8. ↑ Savarese G, De Ferrari GM, Rosano GM, Perrone-Filardi P (December 2015). "Safety and efficacy of ezetimibe: A meta-analysis". International Journal of Cardiology. 201: 247–52. doi:10.1016/j.ijcard.2015.08.103. PMID 26301648.
Retrieved from "https://www.wikidoc.org/index.php?title=NPC1L1&oldid=1533684"