Pleiotropic effects of HNF1A rs1183910 in a population-based study of 60,283 individuals

Kristine H Allin; Børge G Nordestgaard

doi:10.1007/s00125-013-3156-x

Pleiotropic effects of HNF1A rs1183910 in a population-based study of 60,283 individuals

Kristine H Allin, Børge G Nordestgaard

Institut for Klinisk Medicin

7 Citationer (Scopus)

Abstract

AIMS/HYPOTHESIS: According to genome-wide association studies (GWAS) a locus in the HNF1A gene has pleiotropic effects on several metabolic traits. In a large single-centre study we used the intronic variant rs1183910 located in a region with no or low recombination rate as an instrument for the HNF1A locus to evaluate pleiotropic effects of this locus on the risk of developing type 2 diabetes, as well as on body composition and levels of non-fasting glucose, lipids, acute-phase reactants, and biomarkers of liver and pancreas function.

METHODS: We investigated 60,283 individuals from the Danish general population who were all examined in the same laboratory, comprising the Copenhagen General Population Study.

RESULTS: We confirm previous GWAS findings, namely that the minor rs1183910 A allele is associated with an increased risk of developing type 2 diabetes (p(trend) = 0.003), decreased levels of C-reactive protein (CRP; p(trend) = 6 × 10(-76)) and γ-glutamyltransferase (p(trend) = 4 × 10(-48)), and increased levels of total cholesterol (p(trend) = 3 × 10(-10)) and LDL-cholesterol (p(trend) = 3 × 10(-11)). For the first time, we report that the minor rs1183910 A allele is associated with increased levels of non-fasting plasma glucose (p(trend) = 3 × 10(-5)), apolipoprotein B (ApoB; p(trend) = 1 × 10(-4)) and alkaline phosphatase (p(trend) = 5 × 10(-14)), and decreased levels of bilirubin (p trend = 3 × 10(-5)). Our results suggest that the association with increased risk of type 2 diabetes is driven by high non-fasting glucose levels.

CONCLUSIONS/INTERPRETATION: The minor rs1183910 A allele prompts a potential adverse metabolic profile with increased levels of non-fasting glucose, total cholesterol, LDL-cholesterol, ApoB, and alkaline phosphatase, but simultaneously has potential beneficial effects through decreased levels of CRP, γ-glutamyltransferase and bilirubin.

Originalsprog	Engelsk
Tidsskrift	Diabetologia
Vol/bind	57
Udgave nummer	4
Sider (fra-til)	729-737
Antal sider	9
ISSN	0012-186X
DOI	https://doi.org/10.1007/s00125-013-3156-x
Status	Udgivet - apr. 2014

FN’s Verdensmål

Dette resultat bidrager til følgende verdensmål

Adgang til dokumentet

10.1007/s00125-013-3156-x

Citationsformater

@article{b3b5d1073b0c41af8a90c3370087f35a,

title = "Pleiotropic effects of HNF1A rs1183910 in a population-based study of 60,283 individuals",

abstract = "AIMS/HYPOTHESIS: According to genome-wide association studies (GWAS) a locus in the HNF1A gene has pleiotropic effects on several metabolic traits. In a large single-centre study we used the intronic variant rs1183910 located in a region with no or low recombination rate as an instrument for the HNF1A locus to evaluate pleiotropic effects of this locus on the risk of developing type 2 diabetes, as well as on body composition and levels of non-fasting glucose, lipids, acute-phase reactants, and biomarkers of liver and pancreas function.METHODS: We investigated 60,283 individuals from the Danish general population who were all examined in the same laboratory, comprising the Copenhagen General Population Study.RESULTS: We confirm previous GWAS findings, namely that the minor rs1183910 A allele is associated with an increased risk of developing type 2 diabetes (p(trend) = 0.003), decreased levels of C-reactive protein (CRP; p(trend) = 6 × 10(-76)) and γ-glutamyltransferase (p(trend) = 4 × 10(-48)), and increased levels of total cholesterol (p(trend) = 3 × 10(-10)) and LDL-cholesterol (p(trend) = 3 × 10(-11)). For the first time, we report that the minor rs1183910 A allele is associated with increased levels of non-fasting plasma glucose (p(trend) = 3 × 10(-5)), apolipoprotein B (ApoB; p(trend) = 1 × 10(-4)) and alkaline phosphatase (p(trend) = 5 × 10(-14)), and decreased levels of bilirubin (p trend = 3 × 10(-5)). Our results suggest that the association with increased risk of type 2 diabetes is driven by high non-fasting glucose levels.CONCLUSIONS/INTERPRETATION: The minor rs1183910 A allele prompts a potential adverse metabolic profile with increased levels of non-fasting glucose, total cholesterol, LDL-cholesterol, ApoB, and alkaline phosphatase, but simultaneously has potential beneficial effects through decreased levels of CRP, γ-glutamyltransferase and bilirubin.",

keywords = "Aged, Alleles, Apolipoproteins B, Blood Glucose, C-Reactive Protein, Diabetes Mellitus, Type 2, Female, Genome-Wide Association Study, Hepatocyte Nuclear Factor 1-alpha, Humans, Male, Middle Aged, gamma-Glutamyltransferase",

author = "Allin, {Kristine H} and Nordestgaard, {B{\o}rge G}",

year = "2014",

month = apr,

doi = "10.1007/s00125-013-3156-x",

language = "English",

volume = "57",

pages = "729--737",

journal = "Diabetologia",

issn = "0012-186X",

publisher = "Springer",

number = "4",

}

TY - JOUR

T1 - Pleiotropic effects of HNF1A rs1183910 in a population-based study of 60,283 individuals

AU - Allin, Kristine H

AU - Nordestgaard, Børge G

PY - 2014/4

Y1 - 2014/4

N2 - AIMS/HYPOTHESIS: According to genome-wide association studies (GWAS) a locus in the HNF1A gene has pleiotropic effects on several metabolic traits. In a large single-centre study we used the intronic variant rs1183910 located in a region with no or low recombination rate as an instrument for the HNF1A locus to evaluate pleiotropic effects of this locus on the risk of developing type 2 diabetes, as well as on body composition and levels of non-fasting glucose, lipids, acute-phase reactants, and biomarkers of liver and pancreas function.METHODS: We investigated 60,283 individuals from the Danish general population who were all examined in the same laboratory, comprising the Copenhagen General Population Study.RESULTS: We confirm previous GWAS findings, namely that the minor rs1183910 A allele is associated with an increased risk of developing type 2 diabetes (p(trend) = 0.003), decreased levels of C-reactive protein (CRP; p(trend) = 6 × 10(-76)) and γ-glutamyltransferase (p(trend) = 4 × 10(-48)), and increased levels of total cholesterol (p(trend) = 3 × 10(-10)) and LDL-cholesterol (p(trend) = 3 × 10(-11)). For the first time, we report that the minor rs1183910 A allele is associated with increased levels of non-fasting plasma glucose (p(trend) = 3 × 10(-5)), apolipoprotein B (ApoB; p(trend) = 1 × 10(-4)) and alkaline phosphatase (p(trend) = 5 × 10(-14)), and decreased levels of bilirubin (p trend = 3 × 10(-5)). Our results suggest that the association with increased risk of type 2 diabetes is driven by high non-fasting glucose levels.CONCLUSIONS/INTERPRETATION: The minor rs1183910 A allele prompts a potential adverse metabolic profile with increased levels of non-fasting glucose, total cholesterol, LDL-cholesterol, ApoB, and alkaline phosphatase, but simultaneously has potential beneficial effects through decreased levels of CRP, γ-glutamyltransferase and bilirubin.

AB - AIMS/HYPOTHESIS: According to genome-wide association studies (GWAS) a locus in the HNF1A gene has pleiotropic effects on several metabolic traits. In a large single-centre study we used the intronic variant rs1183910 located in a region with no or low recombination rate as an instrument for the HNF1A locus to evaluate pleiotropic effects of this locus on the risk of developing type 2 diabetes, as well as on body composition and levels of non-fasting glucose, lipids, acute-phase reactants, and biomarkers of liver and pancreas function.METHODS: We investigated 60,283 individuals from the Danish general population who were all examined in the same laboratory, comprising the Copenhagen General Population Study.RESULTS: We confirm previous GWAS findings, namely that the minor rs1183910 A allele is associated with an increased risk of developing type 2 diabetes (p(trend) = 0.003), decreased levels of C-reactive protein (CRP; p(trend) = 6 × 10(-76)) and γ-glutamyltransferase (p(trend) = 4 × 10(-48)), and increased levels of total cholesterol (p(trend) = 3 × 10(-10)) and LDL-cholesterol (p(trend) = 3 × 10(-11)). For the first time, we report that the minor rs1183910 A allele is associated with increased levels of non-fasting plasma glucose (p(trend) = 3 × 10(-5)), apolipoprotein B (ApoB; p(trend) = 1 × 10(-4)) and alkaline phosphatase (p(trend) = 5 × 10(-14)), and decreased levels of bilirubin (p trend = 3 × 10(-5)). Our results suggest that the association with increased risk of type 2 diabetes is driven by high non-fasting glucose levels.CONCLUSIONS/INTERPRETATION: The minor rs1183910 A allele prompts a potential adverse metabolic profile with increased levels of non-fasting glucose, total cholesterol, LDL-cholesterol, ApoB, and alkaline phosphatase, but simultaneously has potential beneficial effects through decreased levels of CRP, γ-glutamyltransferase and bilirubin.

KW - Aged

KW - Alleles

KW - Apolipoproteins B

KW - Blood Glucose

KW - C-Reactive Protein

KW - Diabetes Mellitus, Type 2

KW - Female

KW - Genome-Wide Association Study

KW - Hepatocyte Nuclear Factor 1-alpha

KW - Humans

KW - Male

KW - Middle Aged

KW - gamma-Glutamyltransferase

U2 - 10.1007/s00125-013-3156-x

DO - 10.1007/s00125-013-3156-x

M3 - Journal article

C2 - 24442509

SN - 0012-186X

VL - 57

SP - 729

EP - 737

JO - Diabetologia

JF - Diabetologia

IS - 4

ER -

Pleiotropic effects of HNF1A rs1183910 in a population-based study of 60,283 individuals

Abstract

FN’s Verdensmål

Adgang til dokumentet

Fingeraftryk

Citationsformater