Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

Differential methylation of the type 2 diabetes susceptibility locus KCNQ1 is associated with insulin sensitivity and is predicted by CpG site specific genetic variation

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Associations between birth weight and glucose intolerance in adulthood among Greenlandic Inuit

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Work matters: Diabetes and worklife in the second diabetes attitudes, wishes and needs (DAWN2) study

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. The effect of liraglutide on natriuretic peptides and copeptin in heart failure patients

    Publikation: Bidrag til tidsskriftKonferenceabstrakt i tidsskriftForskningpeer review

  2. High Intrarenal Lactate Production Inhibits the Renal Pseudohypoxic Response to Acutely Induced Hypoxia in Diabetes

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Association of Changes in Inflammation with Changes in Glycemia, Insulin Resistance and Secretion: a DIRECT study based on KORA

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  • RISC consortium
Vis graf over relationer

AIMS: Epigenetic mechanisms regulate gene expression and may influence the pathogenesis of type 2 diabetes through the loss of insulin sensitivity. The aims of this study were to measure variation in DNA methylation at the type 2 diabetes locus KCNQ1 and assess its relationship with metabolic measures and with genotype.

METHODS: DNA methylation from whole blood DNA was quantified using pyrosequencing at 5 CpG sites at the KCNQ1 locus in 510 individuals without diabetes from the 'Relationship between Insulin Sensitivity and Cardiovascular disease' (RISC) cohort. Genotype data was analysed at the same locus in 1119 individuals in the same cohort. Insulin sensitivity was assessed by euglycaemic-hyperinsulinaemic clamp.

RESULTS: DNA methylation at the KCNQ1 locus was inversely associated with insulin sensitivity and serum adiponectin. This association was driven by a methylation-altering Single Nucleotide Polymorphism (SNP) (rs231840) which ablated a methylation site and reduced methylation levels. A second SNP (rs231357), in weak Linkage Disequilibrium (LD) with rs231840, was also associated with insulin sensitivity and DNA methylation. These SNPs have not been previously reported to be associated with type 2 diabetes risk or insulin sensitivity.

CONCLUSION: Evidence indicates that genetic and epigenetic determinants at the KCNQ1 locus influence insulin sensitivity.

OriginalsprogEngelsk
TidsskriftDiabetes Research and Clinical Practice
Vol/bind148
Sider (fra-til)189-199
Antal sider11
ISSN0168-8227
DOI
StatusUdgivet - 1 feb. 2019

ID: 56395355