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The loss-of-function PCSK9 p.R46L genetic variant does not alter glucose homeostasis
Aims/hypothesis Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a critical regulator of cholesterol homeostasis. PCSK9 inhibitors are being actively developed to lower LDL-cholesterol levels. However, there are conflicting data regarding the consequences of Pcsk9 deficiency on glucose homeo...
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| Published in: | Diabetologia 2015-09, Vol.58 (9), p.2051-2055 |
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| container_issue | 9 |
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| container_title | Diabetologia |
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| creator | Bonnefond, Amélie Yengo, Loïc Le May, Cédric Fumeron, Fréderic Marre, Michel Balkau, Beverley Charpentier, Guillaume Franc, Sylvia Froguel, Philippe Cariou, Bertrand |
| description | Aims/hypothesis
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a critical regulator of cholesterol homeostasis. PCSK9 inhibitors are being actively developed to lower LDL-cholesterol levels. However, there are conflicting data regarding the consequences of
Pcsk9
deficiency on glucose homeostasis in mouse models. Here, we analysed in humans the association between the
PCSK9
p.R46L loss-of-function (LOF) variant and (1) glucose homeostasis variables; (2) type 2 diabetes status; and (3) the risk of 9 year incident type 2 diabetes in a prospective study.
Methods
PCSK9
p.R46L was genotyped in 4630 French participants from the Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) prospective study and in 1342 French participants with type 2 diabetes. The association between p.R46L and metabolic traits or type 2 diabetes risk was assessed through linear or logistic regression models adjusted for age, sex and BMI. The association between p.R46L and incident type 2 diabetes was assessed using a Cox regression model adjusted for sex, age and BMI at baseline.
Results
Significant associations (
p
|
| doi_str_mv | 10.1007/s00125-015-3659-8 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_hal_p</sourceid><recordid>TN_cdi_hal_primary_oai_HAL_hal_01830978v1</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3769540461</sourcerecordid><originalsourceid>FETCH-LOGICAL-c519t-e4d468e84dda4b505bc82d1e10740d2097d37ec262e93422e669defb69a33f793</originalsourceid><addsrcrecordid>eNp1kU2LFDEQhoMo7uzqD_AiAS96yFr57M5xGVZXHFB0BG8h06me6aWnMybdC_570_TuIoKnQOqpJ1V5CXnF4ZIDVO8zABeaAddMGm1Z_YSsuJKCgRL1U7Kay4zX5ucZOc_5FgCkVuY5ORMGlFUgV2S7PSDtY84stqydhmbs4kC_rr9_tvR0-U2ZDd3jgGPX0DufOj-MNETMdIgj9f2Iie77qYkZ6SEeMebR5y6_IM9a32d8eX9ekB8frrfrG7b58vHT-mrDGs3tyFAFZWqsVQhe7TToXVOLwJFDpSAIsFWQFTbCCLRSCYHG2IDtzlgvZVtZeUHeLd6D790pdUeffrvoO3dztXHzHfBaFk19xwv7dmFPKf6aMI_u2OUG-94PGKfseAXCaGO1Keibf9DbOKWhbDJTRWmhqgvFF6pJ5fsSto8TcHBzPG6Jpwyh3RyPm3te35un3RHDY8dDHgUQC5BLadhj-uvp_1r_AI2tl38</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1701839078</pqid></control><display><type>article</type><title>The loss-of-function PCSK9 p.R46L genetic variant does not alter glucose homeostasis</title><source>Springer Link</source><creator>Bonnefond, Amélie ; Yengo, Loïc ; Le May, Cédric ; Fumeron, Fréderic ; Marre, Michel ; Balkau, Beverley ; Charpentier, Guillaume ; Franc, Sylvia ; Froguel, Philippe ; Cariou, Bertrand</creator><creatorcontrib>Bonnefond, Amélie ; Yengo, Loïc ; Le May, Cédric ; Fumeron, Fréderic ; Marre, Michel ; Balkau, Beverley ; Charpentier, Guillaume ; Franc, Sylvia ; Froguel, Philippe ; Cariou, Bertrand ; DESIR study group ; for the DESIR study group</creatorcontrib><description>Aims/hypothesis
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a critical regulator of cholesterol homeostasis. PCSK9 inhibitors are being actively developed to lower LDL-cholesterol levels. However, there are conflicting data regarding the consequences of
Pcsk9
deficiency on glucose homeostasis in mouse models. Here, we analysed in humans the association between the
PCSK9
p.R46L loss-of-function (LOF) variant and (1) glucose homeostasis variables; (2) type 2 diabetes status; and (3) the risk of 9 year incident type 2 diabetes in a prospective study.
Methods
PCSK9
p.R46L was genotyped in 4630 French participants from the Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) prospective study and in 1342 French participants with type 2 diabetes. The association between p.R46L and metabolic traits or type 2 diabetes risk was assessed through linear or logistic regression models adjusted for age, sex and BMI. The association between p.R46L and incident type 2 diabetes was assessed using a Cox regression model adjusted for sex, age and BMI at baseline.
Results
Significant associations (
p
< 10
−6
) were found between p.R46L and lower total cholesterol (−0.394 mmol/l), LDL-cholesterol (−0.393 mmol/l) and apolipoprotein B concentrations (−0.099 g/l). However, no significant association was observed between p.R46L and markers of glucose homeostasis (including fasting glucose, fasting insulin, HbA
1c
, HOMA-B, HOMA-IR) or type 2 diabetes risk. Furthermore, no significant association between p.R46L variant and risk of incident type 2 diabetes was observed in DESIR.
Conclusions/interpretation
The
PCSK9
p.R46L LOF variant was not associated with impaired glucose homeostasis in humans. These data are reassuring regarding the safety of PCSK9 inhibitors.</description><identifier>ISSN: 0012-186X</identifier><identifier>EISSN: 1432-0428</identifier><identifier>DOI: 10.1007/s00125-015-3659-8</identifier><identifier>PMID: 26049403</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Adult ; Age Factors ; Apolipoproteins ; Blood Glucose - metabolism ; Body Mass Index ; Cholesterol ; Cholesterol - blood ; Cholesterol - metabolism ; Diabetes ; Diabetes Mellitus, Type 2 - blood ; Endocrinology ; Epidemiology ; Female ; France ; Gene Expression Regulation ; Genetic Variation ; Genotype ; Glucose ; Homeostasis ; Human Physiology ; Humans ; Insulin resistance ; Internal Medicine ; Life Sciences ; Longitudinal Studies ; Low density lipoprotein ; Male ; Medicine ; Medicine & Public Health ; Metabolic Diseases ; Middle Aged ; Proprotein Convertase 9 ; Proprotein Convertases - antagonists & inhibitors ; Proprotein Convertases - blood ; Proprotein Convertases - genetics ; Prospective Studies ; Regression Analysis ; Risk Factors ; Serine Endopeptidases - blood ; Serine Endopeptidases - genetics ; Sex Factors ; Short Communication</subject><ispartof>Diabetologia, 2015-09, Vol.58 (9), p.2051-2055</ispartof><rights>Springer-Verlag Berlin Heidelberg 2015</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c519t-e4d468e84dda4b505bc82d1e10740d2097d37ec262e93422e669defb69a33f793</citedby><cites>FETCH-LOGICAL-c519t-e4d468e84dda4b505bc82d1e10740d2097d37ec262e93422e669defb69a33f793</cites><orcidid>0000-0003-2021-413X ; 0000-0001-6124-5712 ; 0000-0002-1580-8040 ; 0000-0001-9976-3005 ; 0000-0001-5123-7743</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26049403$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-01830978$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Bonnefond, Amélie</creatorcontrib><creatorcontrib>Yengo, Loïc</creatorcontrib><creatorcontrib>Le May, Cédric</creatorcontrib><creatorcontrib>Fumeron, Fréderic</creatorcontrib><creatorcontrib>Marre, Michel</creatorcontrib><creatorcontrib>Balkau, Beverley</creatorcontrib><creatorcontrib>Charpentier, Guillaume</creatorcontrib><creatorcontrib>Franc, Sylvia</creatorcontrib><creatorcontrib>Froguel, Philippe</creatorcontrib><creatorcontrib>Cariou, Bertrand</creatorcontrib><creatorcontrib>DESIR study group</creatorcontrib><creatorcontrib>for the DESIR study group</creatorcontrib><title>The loss-of-function PCSK9 p.R46L genetic variant does not alter glucose homeostasis</title><title>Diabetologia</title><addtitle>Diabetologia</addtitle><addtitle>Diabetologia</addtitle><description>Aims/hypothesis
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a critical regulator of cholesterol homeostasis. PCSK9 inhibitors are being actively developed to lower LDL-cholesterol levels. However, there are conflicting data regarding the consequences of
Pcsk9
deficiency on glucose homeostasis in mouse models. Here, we analysed in humans the association between the
PCSK9
p.R46L loss-of-function (LOF) variant and (1) glucose homeostasis variables; (2) type 2 diabetes status; and (3) the risk of 9 year incident type 2 diabetes in a prospective study.
Methods
PCSK9
p.R46L was genotyped in 4630 French participants from the Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) prospective study and in 1342 French participants with type 2 diabetes. The association between p.R46L and metabolic traits or type 2 diabetes risk was assessed through linear or logistic regression models adjusted for age, sex and BMI. The association between p.R46L and incident type 2 diabetes was assessed using a Cox regression model adjusted for sex, age and BMI at baseline.
Results
Significant associations (
p
< 10
−6
) were found between p.R46L and lower total cholesterol (−0.394 mmol/l), LDL-cholesterol (−0.393 mmol/l) and apolipoprotein B concentrations (−0.099 g/l). However, no significant association was observed between p.R46L and markers of glucose homeostasis (including fasting glucose, fasting insulin, HbA
1c
, HOMA-B, HOMA-IR) or type 2 diabetes risk. Furthermore, no significant association between p.R46L variant and risk of incident type 2 diabetes was observed in DESIR.
Conclusions/interpretation
The
PCSK9
p.R46L LOF variant was not associated with impaired glucose homeostasis in humans. These data are reassuring regarding the safety of PCSK9 inhibitors.</description><subject>Adult</subject><subject>Age Factors</subject><subject>Apolipoproteins</subject><subject>Blood Glucose - metabolism</subject><subject>Body Mass Index</subject><subject>Cholesterol</subject><subject>Cholesterol - blood</subject><subject>Cholesterol - metabolism</subject><subject>Diabetes</subject><subject>Diabetes Mellitus, Type 2 - blood</subject><subject>Endocrinology</subject><subject>Epidemiology</subject><subject>Female</subject><subject>France</subject><subject>Gene Expression Regulation</subject><subject>Genetic Variation</subject><subject>Genotype</subject><subject>Glucose</subject><subject>Homeostasis</subject><subject>Human Physiology</subject><subject>Humans</subject><subject>Insulin resistance</subject><subject>Internal Medicine</subject><subject>Life Sciences</subject><subject>Longitudinal Studies</subject><subject>Low density lipoprotein</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metabolic Diseases</subject><subject>Middle Aged</subject><subject>Proprotein Convertase 9</subject><subject>Proprotein Convertases - antagonists & inhibitors</subject><subject>Proprotein Convertases - blood</subject><subject>Proprotein Convertases - genetics</subject><subject>Prospective Studies</subject><subject>Regression Analysis</subject><subject>Risk Factors</subject><subject>Serine Endopeptidases - blood</subject><subject>Serine Endopeptidases - genetics</subject><subject>Sex Factors</subject><subject>Short Communication</subject><issn>0012-186X</issn><issn>1432-0428</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><recordid>eNp1kU2LFDEQhoMo7uzqD_AiAS96yFr57M5xGVZXHFB0BG8h06me6aWnMybdC_570_TuIoKnQOqpJ1V5CXnF4ZIDVO8zABeaAddMGm1Z_YSsuJKCgRL1U7Kay4zX5ucZOc_5FgCkVuY5ORMGlFUgV2S7PSDtY84stqydhmbs4kC_rr9_tvR0-U2ZDd3jgGPX0DufOj-MNETMdIgj9f2Iie77qYkZ6SEeMebR5y6_IM9a32d8eX9ekB8frrfrG7b58vHT-mrDGs3tyFAFZWqsVQhe7TToXVOLwJFDpSAIsFWQFTbCCLRSCYHG2IDtzlgvZVtZeUHeLd6D790pdUeffrvoO3dztXHzHfBaFk19xwv7dmFPKf6aMI_u2OUG-94PGKfseAXCaGO1Keibf9DbOKWhbDJTRWmhqgvFF6pJ5fsSto8TcHBzPG6Jpwyh3RyPm3te35un3RHDY8dDHgUQC5BLadhj-uvp_1r_AI2tl38</recordid><startdate>20150901</startdate><enddate>20150901</enddate><creator>Bonnefond, Amélie</creator><creator>Yengo, Loïc</creator><creator>Le May, Cédric</creator><creator>Fumeron, Fréderic</creator><creator>Marre, Michel</creator><creator>Balkau, Beverley</creator><creator>Charpentier, Guillaume</creator><creator>Franc, Sylvia</creator><creator>Froguel, Philippe</creator><creator>Cariou, Bertrand</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><general>Springer Verlag</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>1XC</scope><orcidid>https://orcid.org/0000-0003-2021-413X</orcidid><orcidid>https://orcid.org/0000-0001-6124-5712</orcidid><orcidid>https://orcid.org/0000-0002-1580-8040</orcidid><orcidid>https://orcid.org/0000-0001-9976-3005</orcidid><orcidid>https://orcid.org/0000-0001-5123-7743</orcidid></search><sort><creationdate>20150901</creationdate><title>The loss-of-function PCSK9 p.R46L genetic variant does not alter glucose homeostasis</title><author>Bonnefond, Amélie ; Yengo, Loïc ; Le May, Cédric ; Fumeron, Fréderic ; Marre, Michel ; Balkau, Beverley ; Charpentier, Guillaume ; Franc, Sylvia ; Froguel, Philippe ; Cariou, Bertrand</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c519t-e4d468e84dda4b505bc82d1e10740d2097d37ec262e93422e669defb69a33f793</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adult</topic><topic>Age Factors</topic><topic>Apolipoproteins</topic><topic>Blood Glucose - metabolism</topic><topic>Body Mass Index</topic><topic>Cholesterol</topic><topic>Cholesterol - blood</topic><topic>Cholesterol - metabolism</topic><topic>Diabetes</topic><topic>Diabetes Mellitus, Type 2 - blood</topic><topic>Endocrinology</topic><topic>Epidemiology</topic><topic>Female</topic><topic>France</topic><topic>Gene Expression Regulation</topic><topic>Genetic Variation</topic><topic>Genotype</topic><topic>Glucose</topic><topic>Homeostasis</topic><topic>Human Physiology</topic><topic>Humans</topic><topic>Insulin resistance</topic><topic>Internal Medicine</topic><topic>Life Sciences</topic><topic>Longitudinal Studies</topic><topic>Low density lipoprotein</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metabolic Diseases</topic><topic>Middle Aged</topic><topic>Proprotein Convertase 9</topic><topic>Proprotein Convertases - antagonists & inhibitors</topic><topic>Proprotein Convertases - blood</topic><topic>Proprotein Convertases - genetics</topic><topic>Prospective Studies</topic><topic>Regression Analysis</topic><topic>Risk Factors</topic><topic>Serine Endopeptidases - blood</topic><topic>Serine Endopeptidases - genetics</topic><topic>Sex Factors</topic><topic>Short Communication</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bonnefond, Amélie</creatorcontrib><creatorcontrib>Yengo, Loïc</creatorcontrib><creatorcontrib>Le May, Cédric</creatorcontrib><creatorcontrib>Fumeron, Fréderic</creatorcontrib><creatorcontrib>Marre, Michel</creatorcontrib><creatorcontrib>Balkau, Beverley</creatorcontrib><creatorcontrib>Charpentier, Guillaume</creatorcontrib><creatorcontrib>Franc, Sylvia</creatorcontrib><creatorcontrib>Froguel, Philippe</creatorcontrib><creatorcontrib>Cariou, Bertrand</creatorcontrib><creatorcontrib>DESIR study group</creatorcontrib><creatorcontrib>for the DESIR study group</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>Diabetologia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bonnefond, Amélie</au><au>Yengo, Loïc</au><au>Le May, Cédric</au><au>Fumeron, Fréderic</au><au>Marre, Michel</au><au>Balkau, Beverley</au><au>Charpentier, Guillaume</au><au>Franc, Sylvia</au><au>Froguel, Philippe</au><au>Cariou, Bertrand</au><aucorp>DESIR study group</aucorp><aucorp>for the DESIR study group</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The loss-of-function PCSK9 p.R46L genetic variant does not alter glucose homeostasis</atitle><jtitle>Diabetologia</jtitle><stitle>Diabetologia</stitle><addtitle>Diabetologia</addtitle><date>2015-09-01</date><risdate>2015</risdate><volume>58</volume><issue>9</issue><spage>2051</spage><epage>2055</epage><pages>2051-2055</pages><issn>0012-186X</issn><eissn>1432-0428</eissn><abstract>Aims/hypothesis
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a critical regulator of cholesterol homeostasis. PCSK9 inhibitors are being actively developed to lower LDL-cholesterol levels. However, there are conflicting data regarding the consequences of
Pcsk9
deficiency on glucose homeostasis in mouse models. Here, we analysed in humans the association between the
PCSK9
p.R46L loss-of-function (LOF) variant and (1) glucose homeostasis variables; (2) type 2 diabetes status; and (3) the risk of 9 year incident type 2 diabetes in a prospective study.
Methods
PCSK9
p.R46L was genotyped in 4630 French participants from the Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) prospective study and in 1342 French participants with type 2 diabetes. The association between p.R46L and metabolic traits or type 2 diabetes risk was assessed through linear or logistic regression models adjusted for age, sex and BMI. The association between p.R46L and incident type 2 diabetes was assessed using a Cox regression model adjusted for sex, age and BMI at baseline.
Results
Significant associations (
p
< 10
−6
) were found between p.R46L and lower total cholesterol (−0.394 mmol/l), LDL-cholesterol (−0.393 mmol/l) and apolipoprotein B concentrations (−0.099 g/l). However, no significant association was observed between p.R46L and markers of glucose homeostasis (including fasting glucose, fasting insulin, HbA
1c
, HOMA-B, HOMA-IR) or type 2 diabetes risk. Furthermore, no significant association between p.R46L variant and risk of incident type 2 diabetes was observed in DESIR.
Conclusions/interpretation
The
PCSK9
p.R46L LOF variant was not associated with impaired glucose homeostasis in humans. These data are reassuring regarding the safety of PCSK9 inhibitors.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>26049403</pmid><doi>10.1007/s00125-015-3659-8</doi><tpages>5</tpages><orcidid>https://orcid.org/0000-0003-2021-413X</orcidid><orcidid>https://orcid.org/0000-0001-6124-5712</orcidid><orcidid>https://orcid.org/0000-0002-1580-8040</orcidid><orcidid>https://orcid.org/0000-0001-9976-3005</orcidid><orcidid>https://orcid.org/0000-0001-5123-7743</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Diabetologia, 2015-09, Vol.58 (9), p.2051-2055 |
| issn | 0012-186X 1432-0428 |
| language | eng |
| recordid | cdi_hal_primary_oai_HAL_hal_01830978v1 |
| source | Springer Link |
| subjects | Adult Age Factors Apolipoproteins Blood Glucose - metabolism Body Mass Index Cholesterol Cholesterol - blood Cholesterol - metabolism Diabetes Diabetes Mellitus, Type 2 - blood Endocrinology Epidemiology Female France Gene Expression Regulation Genetic Variation Genotype Glucose Homeostasis Human Physiology Humans Insulin resistance Internal Medicine Life Sciences Longitudinal Studies Low density lipoprotein Male Medicine Medicine & Public Health Metabolic Diseases Middle Aged Proprotein Convertase 9 Proprotein Convertases - antagonists & inhibitors Proprotein Convertases - blood Proprotein Convertases - genetics Prospective Studies Regression Analysis Risk Factors Serine Endopeptidases - blood Serine Endopeptidases - genetics Sex Factors Short Communication |
| title | The loss-of-function PCSK9 p.R46L genetic variant does not alter glucose homeostasis |
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