TY - JOUR
T1 - FHL2 Genetic Polymorphisms and Pro-Diabetogenic Lipid Profile in the Multiethnic HELIUS Cohort
AU - Habibe, Jayron J.
AU - Boulund, Ulrika
AU - Clemente-Olivo, Maria P.
AU - de Vries, Carlie J. M.
AU - Eringa, Etto C.
AU - Nieuwdorp, Max
AU - Ferwerda, Bart
AU - Zwinderman, Koos
AU - van den Born, Bert-Jan H.
AU - Galenkamp, Henrike
AU - van Raalte, Daniel H.
N1 - Funding Information: This research was supported by a grant from the Rembrandt Institute of Cardiovascular Sciences (C.J.M.d.V.) and the Research Institute of Cardiovascular Sciences of Amsterdam UMC (C.J.M.d.V., E.C.E., D.H.v.R, M.N.). M.N. is supported by a ZONMW VICI grant 2020 [number 09150182010020]. U.B. is supported by an ITN Marie Curie BestTreat—Building a Gut Microbiome Engineering Toolbox for In Situ Therapeutic Treatments for Non-alcoholic Fatty Liver Disease (grant number 813781). The HELIUS study was conducted by the Amsterdam University Medical Centers, location AMC, and the Public Health Service of Amsterdam. Both organizations provided core support for HELIUS. The HELIUS study was also funded by the Dutch Heart Foundation, the Netherlands Organization for Health Research and Development (ZonMw), the European Union (FP-7), and the European Fund for the Integration of non-EU immigrants (EIF). We are most grateful to the participants of the HELIUS study and the management team, research nurses, interviewers, research assistants, and other staff who took part in gathering the data for this study. The study reported here was additionally supported by additional grants from Dutch Heart Foundation: 2010T084 (K Stronks), ZonMw: 200500003 (K Stronks), European Union (FP-7): 278901 (K Stronks), and European Fund for the Integration of non-EU immigrants (EIF): 2013EIF013 (K Stronks). Publisher Copyright: © 2023 by the authors.
PY - 2023/3/1
Y1 - 2023/3/1
N2 - Type 2 diabetes mellitus (T2D) is a prevalent disease often accompanied by the occurrence of dyslipidemia. Four and a half LIM domains 2 (FHL2) is a scaffolding protein, whose involvement in metabolic disease has recently been demonstrated. The association of human FHL2 with T2D and dyslipidemia in a multiethnic setting is unknown. Therefore, we used the large multiethnic Amsterdam-based Healthy Life in an Urban Setting (HELIUS) cohort to investigate FHL2 genetic loci and their potential role in T2D and dyslipidemia. Baseline data of 10,056 participants from the HELIUS study were available for analysis. The HELIUS study contained individuals of European Dutch, South Asian Surinamese, African Surinamese, Ghanaian, Turkish, and Moroccan descent living in Amsterdam and were randomly sampled from the municipality register. Nineteen FHL2 polymorphisms were genotyped, and associations with lipid panels and T2D status were investigated. We observed that seven FHL2 polymorphisms associated nominally with a pro-diabetogenic lipid profile including triglyceride (TG), high-density and low-density lipoprotein-cholesterol (HDL-C and LDL-C), and total cholesterol (TC) concentrations, but not with blood glucose concentrations or T2D status in the complete HELIUS cohort upon correcting for age, gender, BMI, and ancestry. Upon stratifying for ethnicity, we observed that only two of the nominally significant associations passed multiple testing adjustments, namely, the association of rs4640402 with increased TG and rs880427 with decreased HDL-C concentrations in the Ghanaian population. Our results highlight the effect of ethnicity on pro-diabetogenic selected lipid biomarkers within the HELIUS cohort, as well as the need for more large multiethnic cohort studies.
AB - Type 2 diabetes mellitus (T2D) is a prevalent disease often accompanied by the occurrence of dyslipidemia. Four and a half LIM domains 2 (FHL2) is a scaffolding protein, whose involvement in metabolic disease has recently been demonstrated. The association of human FHL2 with T2D and dyslipidemia in a multiethnic setting is unknown. Therefore, we used the large multiethnic Amsterdam-based Healthy Life in an Urban Setting (HELIUS) cohort to investigate FHL2 genetic loci and their potential role in T2D and dyslipidemia. Baseline data of 10,056 participants from the HELIUS study were available for analysis. The HELIUS study contained individuals of European Dutch, South Asian Surinamese, African Surinamese, Ghanaian, Turkish, and Moroccan descent living in Amsterdam and were randomly sampled from the municipality register. Nineteen FHL2 polymorphisms were genotyped, and associations with lipid panels and T2D status were investigated. We observed that seven FHL2 polymorphisms associated nominally with a pro-diabetogenic lipid profile including triglyceride (TG), high-density and low-density lipoprotein-cholesterol (HDL-C and LDL-C), and total cholesterol (TC) concentrations, but not with blood glucose concentrations or T2D status in the complete HELIUS cohort upon correcting for age, gender, BMI, and ancestry. Upon stratifying for ethnicity, we observed that only two of the nominally significant associations passed multiple testing adjustments, namely, the association of rs4640402 with increased TG and rs880427 with decreased HDL-C concentrations in the Ghanaian population. Our results highlight the effect of ethnicity on pro-diabetogenic selected lipid biomarkers within the HELIUS cohort, as well as the need for more large multiethnic cohort studies.
KW - FHL2
KW - HELIUS
KW - LDL-C
KW - TG
KW - cohort study
KW - dyslipidemia
KW - polymorphism
UR - http://www.scopus.com/inward/record.url?scp=85149857138&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/ijms24054332
DO - https://doi.org/10.3390/ijms24054332
M3 - Article
C2 - 36901761
SN - 1661-6596
VL - 24
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 5
M1 - 4332
ER -