Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
E-pub ahead of print

The low-expression variant of FABP4 is associated with cardiovascular disease in type 1 diabetes

Research output: Contribution to journalJournal articleResearchpeer-review

DOI

  1. Effects of Dapagliflozin in Patients With Kidney Disease, With and Without Heart Failure

    Research output: Contribution to journalJournal articleResearchpeer-review

  • FinnDiane study group
View graph of relations

Fatty acid binding protein 4 (FABP4) is implicated in the pathogenesis of cardiometabolic disorders. Pharmacological inhibition or genetic deletion of FABP4 improves cardiometabolic health and protects against atherosclerosis in preclinical models. As cardiovascular disease (CVD) is common in type 1 diabetes, we examined the role of FABP4 in the development of complications in type 1 diabetes, focusing on a functional, low-expression variant (rs77878271) in the promoter of the FABP4 gene. For this, we assessed the risk of CVD, stroke, coronary artery disease (CAD), end-stage kidney disease, and mortality using Cox proportional hazards models for the FABP4 rs77878271 in 5,077 Finnish individuals with type 1 diabetes. The low-expression G allele of rs77878271 increased the risk of CVD, independent of confounders. Findings were tested for replication in 852 Danish and 3,678 Finnish individuals with type 1 diabetes. In the meta-analysis, each G allele increased the risk of stroke by 26% (P = 0.04), CAD by 26% (P = 0.006), and CVD by 17% (P = 0.003). In Mendelian randomization, a 1-SD unit decrease in FABP4 increased risk of CAD 2.4-fold. Hence, in contrast with the general population, among patients with type 1 diabetes the low-expression G allele of rs77878271 increased CVD risk, suggesting that genetically low FABP4 levels may be detrimental in the context of type 1 diabetes.

Original languageEnglish
JournalDiabetes
ISSN0012-1797
DOIs
Publication statusE-pub ahead of print - 9 Jul 2021

ID: 66944037