EIF4A2 is a positional candidate gene at the 3q27 locus linked to type 2 diabetes in French families

Claire Cheyssac; Christian Dina; Frédéric Leprêtre; Valérie Vasseur-Delannoy; Aurélie Dechaume; Stéphane Lobbens; Beverley Balkau; Juan Ruiz; Guillaume Charpentier; François Pattou; Erik Joly; Marc Prentki; Torben Hansen; Oluf Pedersen; Martine Vaxillaire; Philippe Froguel

EIF4A2 is a positional candidate gene at the 3q27 locus linked to type 2 diabetes in French families

Claire Cheyssac, Christian Dina, Frédéric Leprêtre, Valérie Vasseur-Delannoy, Aurélie Dechaume, Stéphane Lobbens, Beverley Balkau, Juan Ruiz, Guillaume Charpentier, François Pattou, Erik Joly, Marc Prentki, Torben Hansen, Oluf Pedersen, Martine Vaxillaire, Philippe Froguel

19 Citations (Scopus)

Abstract

One of the most replicated loci influencing type 2 diabetes-related quantitative traits (quantitative trait loci [QTL]) is on chromosome 3q27 and modulates both type 2 diabetes-and metabolic syndrome-associated phenotypes. A QTL for type 2 diabetes age of onset (logarithm of odds [LOD] score = 3.01 at D3S3686, P = 0.0001) was identified in a set of French families. To assess genetic variation underlying both age-of-onset QTL and our previous type 2 diabetes linkage in a 3.87-Mb interval, we explored 36 single nucleotide polymorphisms (SNPs) in two biologically relevant candidate genes for glucose homeostasis, kininogen (KNG1), and eukaryotic translation initiation factor 4alpha2 (EIF4A2). Analysis of 148 families showed significant association of a frequent SNP, rs266714, located 2.47 kb upstream of EIF4A2, with familial type 2 diabetes (family-based association test, P = 0.0008) and early age of onset (P = 0.0008). This SNP also contributes to both age-of-onset QTL (1.13 LOD score decrease P = 0.02) and type 2 diabetes linkage (genotype identical-by-descent sharing test, P = 0.02). However, no association was observed in three independent European diabetic cohorts. EIF4A2 controls specific mRNA translation and protein synthesis rate in pancreatic beta-cells, and our data indicates that EIF4A2 is downregulated by high glucose in rat beta-INS832/13 cells. The potential role of EIF4A2 in glucose homeostasis and its putative contribution to type 2 diabetes in the presence of metabolic stress will require further investigation.

Original language	English
Journal	Diabetes
Volume	55
Issue number	4
Pages (from-to)	1171-6
Number of pages	6
ISSN	0012-1797
Publication status	Published - 2006

Keywords

Age of Onset
Chromosome Mapping
Chromosomes, Human, Pair 3
Diabetes Mellitus, Type 2
Eukaryotic Initiation Factor-4A
Female
France
Genes, Dominant
Genes, Recessive
Humans
Kininogens
Male
Nuclear Family
Polymorphism, Single Nucleotide
Quantitative Trait Loci
Sex Ratio

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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title = "EIF4A2 is a positional candidate gene at the 3q27 locus linked to type 2 diabetes in French families",

abstract = "One of the most replicated loci influencing type 2 diabetes-related quantitative traits (quantitative trait loci [QTL]) is on chromosome 3q27 and modulates both type 2 diabetes-and metabolic syndrome-associated phenotypes. A QTL for type 2 diabetes age of onset (logarithm of odds [LOD] score = 3.01 at D3S3686, P = 0.0001) was identified in a set of French families. To assess genetic variation underlying both age-of-onset QTL and our previous type 2 diabetes linkage in a 3.87-Mb interval, we explored 36 single nucleotide polymorphisms (SNPs) in two biologically relevant candidate genes for glucose homeostasis, kininogen (KNG1), and eukaryotic translation initiation factor 4alpha2 (EIF4A2). Analysis of 148 families showed significant association of a frequent SNP, rs266714, located 2.47 kb upstream of EIF4A2, with familial type 2 diabetes (family-based association test, P = 0.0008) and early age of onset (P = 0.0008). This SNP also contributes to both age-of-onset QTL (1.13 LOD score decrease P = 0.02) and type 2 diabetes linkage (genotype identical-by-descent sharing test, P = 0.02). However, no association was observed in three independent European diabetic cohorts. EIF4A2 controls specific mRNA translation and protein synthesis rate in pancreatic beta-cells, and our data indicates that EIF4A2 is downregulated by high glucose in rat beta-INS832/13 cells. The potential role of EIF4A2 in glucose homeostasis and its putative contribution to type 2 diabetes in the presence of metabolic stress will require further investigation.",

keywords = "Age of Onset, Chromosome Mapping, Chromosomes, Human, Pair 3, Diabetes Mellitus, Type 2, Eukaryotic Initiation Factor-4A, Female, France, Genes, Dominant, Genes, Recessive, Humans, Kininogens, Male, Nuclear Family, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Sex Ratio",

author = "Claire Cheyssac and Christian Dina and Fr{\'e}d{\'e}ric Lepr{\^e}tre and Val{\'e}rie Vasseur-Delannoy and Aur{\'e}lie Dechaume and St{\'e}phane Lobbens and Beverley Balkau and Juan Ruiz and Guillaume Charpentier and Fran{\c c}ois Pattou and Erik Joly and Marc Prentki and Torben Hansen and Oluf Pedersen and Martine Vaxillaire and Philippe Froguel",

year = "2006",

language = "English",

volume = "55",

pages = "1171--6",

journal = "Diabetes",

issn = "0012-1797",

publisher = "American Diabetes Association",

number = "4",

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TY - JOUR

T1 - EIF4A2 is a positional candidate gene at the 3q27 locus linked to type 2 diabetes in French families

AU - Cheyssac, Claire

AU - Dina, Christian

AU - Leprêtre, Frédéric

AU - Vasseur-Delannoy, Valérie

AU - Dechaume, Aurélie

AU - Lobbens, Stéphane

AU - Balkau, Beverley

AU - Ruiz, Juan

AU - Charpentier, Guillaume

AU - Pattou, François

AU - Joly, Erik

AU - Prentki, Marc

AU - Hansen, Torben

AU - Pedersen, Oluf

AU - Vaxillaire, Martine

AU - Froguel, Philippe

PY - 2006

Y1 - 2006

N2 - One of the most replicated loci influencing type 2 diabetes-related quantitative traits (quantitative trait loci [QTL]) is on chromosome 3q27 and modulates both type 2 diabetes-and metabolic syndrome-associated phenotypes. A QTL for type 2 diabetes age of onset (logarithm of odds [LOD] score = 3.01 at D3S3686, P = 0.0001) was identified in a set of French families. To assess genetic variation underlying both age-of-onset QTL and our previous type 2 diabetes linkage in a 3.87-Mb interval, we explored 36 single nucleotide polymorphisms (SNPs) in two biologically relevant candidate genes for glucose homeostasis, kininogen (KNG1), and eukaryotic translation initiation factor 4alpha2 (EIF4A2). Analysis of 148 families showed significant association of a frequent SNP, rs266714, located 2.47 kb upstream of EIF4A2, with familial type 2 diabetes (family-based association test, P = 0.0008) and early age of onset (P = 0.0008). This SNP also contributes to both age-of-onset QTL (1.13 LOD score decrease P = 0.02) and type 2 diabetes linkage (genotype identical-by-descent sharing test, P = 0.02). However, no association was observed in three independent European diabetic cohorts. EIF4A2 controls specific mRNA translation and protein synthesis rate in pancreatic beta-cells, and our data indicates that EIF4A2 is downregulated by high glucose in rat beta-INS832/13 cells. The potential role of EIF4A2 in glucose homeostasis and its putative contribution to type 2 diabetes in the presence of metabolic stress will require further investigation.

AB - One of the most replicated loci influencing type 2 diabetes-related quantitative traits (quantitative trait loci [QTL]) is on chromosome 3q27 and modulates both type 2 diabetes-and metabolic syndrome-associated phenotypes. A QTL for type 2 diabetes age of onset (logarithm of odds [LOD] score = 3.01 at D3S3686, P = 0.0001) was identified in a set of French families. To assess genetic variation underlying both age-of-onset QTL and our previous type 2 diabetes linkage in a 3.87-Mb interval, we explored 36 single nucleotide polymorphisms (SNPs) in two biologically relevant candidate genes for glucose homeostasis, kininogen (KNG1), and eukaryotic translation initiation factor 4alpha2 (EIF4A2). Analysis of 148 families showed significant association of a frequent SNP, rs266714, located 2.47 kb upstream of EIF4A2, with familial type 2 diabetes (family-based association test, P = 0.0008) and early age of onset (P = 0.0008). This SNP also contributes to both age-of-onset QTL (1.13 LOD score decrease P = 0.02) and type 2 diabetes linkage (genotype identical-by-descent sharing test, P = 0.02). However, no association was observed in three independent European diabetic cohorts. EIF4A2 controls specific mRNA translation and protein synthesis rate in pancreatic beta-cells, and our data indicates that EIF4A2 is downregulated by high glucose in rat beta-INS832/13 cells. The potential role of EIF4A2 in glucose homeostasis and its putative contribution to type 2 diabetes in the presence of metabolic stress will require further investigation.

KW - Age of Onset

KW - Chromosome Mapping

KW - Chromosomes, Human, Pair 3

KW - Diabetes Mellitus, Type 2

KW - Eukaryotic Initiation Factor-4A

KW - Female

KW - France

KW - Genes, Dominant

KW - Genes, Recessive

KW - Humans

KW - Kininogens

KW - Male

KW - Nuclear Family

KW - Polymorphism, Single Nucleotide

KW - Quantitative Trait Loci

KW - Sex Ratio

M3 - Journal article

C2 - 16567544

SN - 0012-1797

VL - 55

SP - 1171

EP - 1176

JO - Diabetes

JF - Diabetes

IS - 4

ER -

EIF4A2 is a positional candidate gene at the 3q27 locus linked to type 2 diabetes in French families

Abstract

Keywords

UN SDGs

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