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

Pavel Hamet, Mounsif Haloui, François Harvey, François Christophe Marois-Blanchet, Marie Pierre Sylvestre, Muhammad Ramzan Tahir, Paul H G Simon, Beatriz Sonja Kanzki, John Raelson, Carole Long, John Chalmers, Mark Woodward, Michel Marre, Stephen Harrap, Johanne Tremblay

Research output: Contribution to journalArticle

Abstract

BACKGROUND:: 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. METHODS:: 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. RESULTS:: 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 (P?=?7.3?×?10), whereas the prevalence of hypertension (P?=?4.9?×?10) and albuminuria (5.1?×?10) 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 PROX1/PROX1-AS1 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. CONCLUSION:: These results reveal the presence of distinct genetic architectures between Caucasian ethnic groups that likely have clinical relevance, among them PROX1 gene is a strong candidate of early onset of diabetes with variations depending on ethnicity.

Original languageEnglish (US)
JournalJournal of Hypertension
DOIs
StateAccepted/In press - Jan 5 2017
Externally publishedYes

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perindopril drug combination indapamide
Gliclazide
Vascular Diseases
Age of Onset
Type 2 Diabetes Mellitus
Genotype
Albuminuria
Genome-Wide Association Study
Diabetic Nephropathies
Ethnic Groups
Genes
Principal Component Analysis
Population
Single Nucleotide Polymorphism
Hypertension

ASJC Scopus subject areas

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

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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. / Hamet, Pavel; Haloui, Mounsif; Harvey, François; Marois-Blanchet, François Christophe; Sylvestre, Marie Pierre; Tahir, Muhammad Ramzan; Simon, Paul H G; Kanzki, Beatriz Sonja; Raelson, John; Long, Carole; Chalmers, John; Woodward, Mark; Marre, Michel; Harrap, Stephen; Tremblay, Johanne.

In: Journal of Hypertension, 05.01.2017.

Research output: Contribution to journalArticle

Hamet, P, Haloui, M, Harvey, F, Marois-Blanchet, FC, Sylvestre, MP, Tahir, MR, Simon, PHG, Kanzki, BS, Raelson, J, Long, C, Chalmers, J, Woodward, M, Marre, M, Harrap, S & Tremblay, J 2017, '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', Journal of Hypertension. https://doi.org/10.1097/HJH.0000000000001241
Hamet, Pavel ; Haloui, Mounsif ; Harvey, François ; Marois-Blanchet, François Christophe ; Sylvestre, Marie Pierre ; Tahir, Muhammad Ramzan ; Simon, Paul H G ; Kanzki, Beatriz Sonja ; Raelson, John ; Long, Carole ; Chalmers, John ; Woodward, Mark ; Marre, Michel ; Harrap, Stephen ; Tremblay, Johanne. / 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. In: Journal of Hypertension. 2017.
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abstract = "BACKGROUND:: 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. METHODS:: 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. RESULTS:: 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 (P?=?7.3?×?10), whereas the prevalence of hypertension (P?=?4.9?×?10) and albuminuria (5.1?×?10) 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 PROX1/PROX1-AS1 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. CONCLUSION:: These results reveal the presence of distinct genetic architectures between Caucasian ethnic groups that likely have clinical relevance, among them PROX1 gene is a strong candidate of early onset of diabetes with variations depending on ethnicity.",
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T1 - 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

T2 - Preterax and Diamicron MR Controlled Evaluation study

AU - Hamet, Pavel

AU - Haloui, Mounsif

AU - Harvey, François

AU - Marois-Blanchet, François Christophe

AU - Sylvestre, Marie Pierre

AU - Tahir, Muhammad Ramzan

AU - Simon, Paul H G

AU - Kanzki, Beatriz Sonja

AU - Raelson, John

AU - Long, Carole

AU - Chalmers, John

AU - Woodward, Mark

AU - Marre, Michel

AU - Harrap, Stephen

AU - Tremblay, Johanne

PY - 2017/1/5

Y1 - 2017/1/5

N2 - BACKGROUND:: 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. METHODS:: 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. RESULTS:: 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 (P?=?7.3?×?10), whereas the prevalence of hypertension (P?=?4.9?×?10) and albuminuria (5.1?×?10) 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 PROX1/PROX1-AS1 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. CONCLUSION:: These results reveal the presence of distinct genetic architectures between Caucasian ethnic groups that likely have clinical relevance, among them PROX1 gene is a strong candidate of early onset of diabetes with variations depending on ethnicity.

AB - BACKGROUND:: 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. METHODS:: 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. RESULTS:: 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 (P?=?7.3?×?10), whereas the prevalence of hypertension (P?=?4.9?×?10) and albuminuria (5.1?×?10) 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 PROX1/PROX1-AS1 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. CONCLUSION:: These results reveal the presence of distinct genetic architectures between Caucasian ethnic groups that likely have clinical relevance, among them PROX1 gene is a strong candidate of early onset of diabetes with variations depending on ethnicity.

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