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

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FinnDiane study group. / The low-expression variant of FABP4 is associated with cardiovascular disease in type 1 diabetes. In: Diabetes. 2021 ; Vol. 70, No. 10. pp. 2391-2401.

Bibtex

@article{5b89e34fb48549859f79aaee2de76d1f,
title = "The low-expression variant of FABP4 is associated with cardiovascular disease in type 1 diabetes",
abstract = "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.",
author = "Dahlstr{\"o}m, {Emma H} and Jani Saksi and Carol Forsblom and Nicoline Uglebjerg and Nina Mars and Thorn, {Lena M} and Valma Harjutsalo and Peter Rossing and Ahluwalia, {Tarunveer S} and Lindsberg, {Perttu J} and Niina Sandholm and Per-Henrik Groop and {FinnDiane study group}",
note = "{\textcopyright} 2021 by the American Diabetes Association.",
year = "2021",
month = oct,
doi = "10.2337/db21-0056",
language = "English",
volume = "70",
pages = "2391--2401",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association",
number = "10",

}

RIS

TY - JOUR

T1 - The low-expression variant of FABP4 is associated with cardiovascular disease in type 1 diabetes

AU - Dahlström, Emma H

AU - Saksi, Jani

AU - Forsblom, Carol

AU - Uglebjerg, Nicoline

AU - Mars, Nina

AU - Thorn, Lena M

AU - Harjutsalo, Valma

AU - Rossing, Peter

AU - Ahluwalia, Tarunveer S

AU - Lindsberg, Perttu J

AU - Sandholm, Niina

AU - Groop, Per-Henrik

AU - FinnDiane study group

N1 - © 2021 by the American Diabetes Association.

PY - 2021/10

Y1 - 2021/10

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85115844778&partnerID=8YFLogxK

U2 - 10.2337/db21-0056

DO - 10.2337/db21-0056

M3 - Journal article

C2 - 34244239

VL - 70

SP - 2391

EP - 2401

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 10

ER -

ID: 66944037