PROX1 gene CC genotype as a major determinant of early onset of type 2 diabetes in slavic study participants from Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation study
Identifieur interne : 001324 ( Main/Curation ); précédent : 001323; suivant : 001325PROX1 gene CC genotype as a major determinant of early onset of type 2 diabetes in slavic study participants from Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation study
Auteurs : Pavel Hamet ; Mounsif Haloui ; François Harvey ; François-Christophe Marois-Blanchet ; Marie-Pierre Sylvestre ; Muhammad-Ramzan Tahir ; Paul H. G. Simon ; Beatriz Sonja Kanzki [Canada] ; John Raelson ; Carole Long ; John Chalmers [Australie] ; Mark Woodward [Australie] ; Michel Marre [France] ; Stephen Harrap [Australie] ; Johanne TremblaySource :
- Journal of Hypertension [ 0263-6352 ] ; 2017.
Descripteurs français
- KwdFr :
- Adulte d'âge moyen, Albuminurie (ethnologie), Albuminurie (génétique), Diabète de type 2 (ethnologie), Diabète de type 2 (génétique), Femelle, Groupes ethniques (génétique), Génotype, Humains, Hypertension artérielle (ethnologie), Mâle, Néphropathies diabétiques (ethnologie), Néphropathies diabétiques (génétique), Polymorphisme de nucléotide simple, Population d'origine européenne (génétique), Protéines suppresseurs de tumeurs (génétique), Protéines à homéodomaine (génétique), Sujet âgé, Âge de début, Étude d'association pangénomique.
- MESH :
- ethnologie : Albuminurie, Diabète de type 2, Hypertension artérielle, Néphropathies diabétiques.
- génétique : Albuminurie, Diabète de type 2, Groupes ethniques, Néphropathies diabétiques, Population d'origine européenne, Protéines suppresseurs de tumeurs, Protéines à homéodomaine.
- Adulte d'âge moyen, Femelle, Génotype, Humains, Mâle, Polymorphisme de nucléotide simple, Sujet âgé, Âge de début, Étude d'association pangénomique.
English descriptors
- KwdEn :
- Age of Onset, Aged, Albuminuria (ethnology), Albuminuria (genetics), Diabetes Mellitus, Type 2 (ethnology), Diabetes Mellitus, Type 2 (genetics), Diabetic Nephropathies (ethnology), Diabetic Nephropathies (genetics), Ethnic Groups (genetics), European Continental Ancestry Group (genetics), Female, Genome-Wide Association Study, Genotype, Homeodomain Proteins (genetics), Humans, Hypertension (ethnology), Male, Middle Aged, Polymorphism, Single Nucleotide, Tumor Suppressor Proteins (genetics).
- MESH :
- chemical , genetics : Homeodomain Proteins, Tumor Suppressor Proteins.
- ethnology : Albuminuria, Diabetes Mellitus, Type 2, Diabetic Nephropathies, Hypertension.
- genetics : Albuminuria, Diabetes Mellitus, Type 2, Diabetic Nephropathies, Ethnic Groups, European Continental Ancestry Group.
- Age of Onset, Aged, Female, Genome-Wide Association Study, Genotype, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide.
Abstract
The prevalence of diabetic nephropathy varies according to ethnicity. Environmental as well as genetic factors contribute to the heterogeneity in the presentation of diabetic nephropathy. Our objective was to evaluate this heterogeneity within the Caucasian population.
The geo-ethnic origin of the 3409 genotyped Caucasian type 2 diabetes (T2D) patients of Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation was determined using principal component analysis. Genome-wide association studies analyses of age of onset of T2D were performed for geo-ethnic groups separately and combined.
The first principal component separated the Caucasian study participants into Slavic and Celtic ethnic origins. Age of onset of diabetes was significantly lower in Slavic patients (
These results reveal the presence of distinct genetic architectures between Caucasian ethnic groups that likely have clinical relevance, among them
Url:
DOI: 10.1097/HJH.0000000000001241
PubMed: 28060188
PubMed Central: 5377997
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Pavel Hamet<affiliation><nlm:aff id="aff1">Department of Medicine, Gene Medicine Services</nlm:aff>
<wicri:noCountry code="subfield">Gene Medicine Services</wicri:noCountry>
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<affiliation><nlm:aff id="aff2">Department of Medicine</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff3">Department of Social and Preventive Medicine, Université de Montréal, CRCHUM</nlm:aff>
<wicri:noCountry code="subfield">CRCHUM</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="aff1">Department of Medicine, Gene Medicine Services</nlm:aff>
<wicri:noCountry code="subfield">Gene Medicine Services</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="aff2">Department of Medicine</nlm:aff>
</affiliation>
Le document en format XML
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gene CC genotype as a major determinant of early onset of type 2 diabetes in slavic study participants from Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation study</title>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main"><italic>PROX1</italic>
gene CC genotype as a major determinant of early onset of type 2 diabetes in slavic study participants from Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation study</title>
<author><name sortKey="Hamet, Pavel" sort="Hamet, Pavel" uniqKey="Hamet P" first="Pavel" last="Hamet">Pavel Hamet</name>
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<author><name sortKey="Tahir, Muhammad Ramzan" sort="Tahir, Muhammad Ramzan" uniqKey="Tahir M" first="Muhammad-Ramzan" last="Tahir">Muhammad-Ramzan Tahir</name>
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<author><name sortKey="Raelson, John" sort="Raelson, John" uniqKey="Raelson J" first="John" last="Raelson">John Raelson</name>
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<author><name sortKey="Long, Carole" sort="Long, Carole" uniqKey="Long C" first="Carole" last="Long">Carole Long</name>
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<author><name sortKey="Chalmers, John" sort="Chalmers, John" uniqKey="Chalmers J" first="John" last="Chalmers">John Chalmers</name>
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<author><name sortKey="Woodward, Mark" sort="Woodward, Mark" uniqKey="Woodward M" first="Mark" last="Woodward">Mark Woodward</name>
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<author><name sortKey="Marre, Michel" sort="Marre, Michel" uniqKey="Marre M" first="Michel" last="Marre">Michel Marre</name>
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<term>Aged</term>
<term>Albuminuria (ethnology)</term>
<term>Albuminuria (genetics)</term>
<term>Diabetes Mellitus, Type 2 (ethnology)</term>
<term>Diabetes Mellitus, Type 2 (genetics)</term>
<term>Diabetic Nephropathies (ethnology)</term>
<term>Diabetic Nephropathies (genetics)</term>
<term>Ethnic Groups (genetics)</term>
<term>European Continental Ancestry Group (genetics)</term>
<term>Female</term>
<term>Genome-Wide Association Study</term>
<term>Genotype</term>
<term>Homeodomain Proteins (genetics)</term>
<term>Humans</term>
<term>Hypertension (ethnology)</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Polymorphism, Single Nucleotide</term>
<term>Tumor Suppressor Proteins (genetics)</term>
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<term>Albuminurie (ethnologie)</term>
<term>Albuminurie (génétique)</term>
<term>Diabète de type 2 (ethnologie)</term>
<term>Diabète de type 2 (génétique)</term>
<term>Femelle</term>
<term>Groupes ethniques (génétique)</term>
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<term>Humains</term>
<term>Hypertension artérielle (ethnologie)</term>
<term>Mâle</term>
<term>Néphropathies diabétiques (ethnologie)</term>
<term>Néphropathies diabétiques (génétique)</term>
<term>Polymorphisme de nucléotide simple</term>
<term>Population d'origine européenne (génétique)</term>
<term>Protéines suppresseurs de tumeurs (génétique)</term>
<term>Protéines à homéodomaine (génétique)</term>
<term>Sujet âgé</term>
<term>Âge de début</term>
<term>Étude d'association pangénomique</term>
</keywords>
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<term>Tumor Suppressor Proteins</term>
</keywords>
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<term>Diabète de type 2</term>
<term>Hypertension artérielle</term>
<term>Néphropathies diabétiques</term>
</keywords>
<keywords scheme="MESH" qualifier="ethnology" xml:lang="en"><term>Albuminuria</term>
<term>Diabetes Mellitus, Type 2</term>
<term>Diabetic Nephropathies</term>
<term>Hypertension</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Albuminuria</term>
<term>Diabetes Mellitus, Type 2</term>
<term>Diabetic Nephropathies</term>
<term>Ethnic Groups</term>
<term>European Continental Ancestry Group</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Albuminurie</term>
<term>Diabète de type 2</term>
<term>Groupes ethniques</term>
<term>Néphropathies diabétiques</term>
<term>Population d'origine européenne</term>
<term>Protéines suppresseurs de tumeurs</term>
<term>Protéines à homéodomaine</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Age of Onset</term>
<term>Aged</term>
<term>Female</term>
<term>Genome-Wide Association Study</term>
<term>Genotype</term>
<term>Humans</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Polymorphism, Single Nucleotide</term>
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<term>Femelle</term>
<term>Génotype</term>
<term>Humains</term>
<term>Mâle</term>
<term>Polymorphisme de nucléotide simple</term>
<term>Sujet âgé</term>
<term>Âge de début</term>
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</teiHeader>
<front><div type="abstract" xml:lang="en"><sec sec-type="background"><title>Background:</title>
<p>The prevalence of diabetic nephropathy varies according to ethnicity. Environmental as well as genetic factors contribute to the heterogeneity in the presentation of diabetic nephropathy. Our objective was to evaluate this heterogeneity within the Caucasian population.</p>
</sec>
<sec sec-type="methods"><title>Methods:</title>
<p>The geo-ethnic origin of the 3409 genotyped Caucasian type 2 diabetes (T2D) patients of Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation was determined using principal component analysis. Genome-wide association studies analyses of age of onset of T2D were performed for geo-ethnic groups separately and combined.</p>
</sec>
<sec sec-type="results"><title>Results:</title>
<p>The first principal component separated the Caucasian study participants into Slavic and Celtic ethnic origins. Age of onset of diabetes was significantly lower in Slavic patients (<italic>P</italic>
= 7.3 × 10<sup>−20</sup>
), whereas the prevalence of hypertension (<italic>P</italic>
= 4.9 × 10<sup>−31</sup>
) and albuminuria (5.1 × 10<sup>−9</sup>
) were significantly higher. Age of onset of T2D and albuminuria appear to have an important genetic component as the values of these traits were also different between Slavic and Celtic individuals living in the same countries. Common and geo-ethnic-specific loci were found to be associated to age of onset of diabetes. Among the latter, the <italic>PROX1/PROX1-AS1</italic>
genes (rs340841) had the highest impact. Single-nucleotide polymorphism rs340841 CC genotype was associated with a 4.4 year earlier onset of T2D in Slavic patients living or not in countries with predominant Slavic populations.</p>
</sec>
<sec sec-type="conclusion"><title>Conclusion:</title>
<p>These results reveal the presence of distinct genetic architectures between Caucasian ethnic groups that likely have clinical relevance, among them <italic>PROX1</italic>
gene is a strong candidate of early onset of diabetes with variations depending on ethnicity.</p>
</sec>
</div>
</front>
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