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Clinical Research

The association between vitamin D receptor polymorphisms and tissue-specific insulin resistance in human obesity

International Journal of Obesity volume 45, pages 818–827 (2021)Cite this article

Subjects

Abstract

Background/objectives

To investigate (1) the association of four VDR polymorphisms (TaqI/rs731236, ApaI/rs7975232, FokI/rs10735810, and Bsml/rs1544410) with markers of adiposity and tissue-specific insulin resistance at baseline, after weight loss and weight maintenance; (2) the effect of the VDR polymorphisms in the SAT transcriptome in overweight/obese Caucasians of the DiOGenes cohort.

Methods

We included 553 adult obese individuals (mean BMI 34.8 kg/m2), men (n = 197) and women (n = 356) at baseline, following an 8-week weight loss intervention and 26 weeks weight maintenance. Genotyping was performed using an Illumina 660W-Quad SNP chip on the Illumina iScan Genotyping System. Tissue-specific IR was determined using Hepatic Insulin Resistance Index (HIRI), Muscle Insulin Sensitivity Index (MISI), and Adipose Tissue Insulin Resistance Index (Adipo-IR). Expression quantitative trait loci (eQTL) analysis was performed to determine the effect of SNPs on SAT gene expression.

Results

None of the VDR polymorphisms were associated with HIRI or MISI. Interestingly, carriers of the G allele of VDR FokI showed higher Adipo-IR (GG + GA 7.8 ± 0.4 vs. AA 5.6 ± 0.5, P = 0.010) and higher systemic FFA (GG + GA: 637.8 ± 13.4 vs. AA: 547.9 ± 24.7 µmol/L, P = 0.011), even after adjustment with age, sex, center, and FM. However, eQTL analysis showed minor to no effect of these genotypes on the transcriptional level in SAT. Also, VDR polymorphisms were not related to changes in body weight and IR as result of dietary intervention (P > 0.05 for all parameters).

Conclusions

The VDR Fokl variant is associated with elevated circulating FFA and Adipo-IR at baseline. Nevertheless, minor to no effect of VDR SNPs on the transcriptional level in SAT, indicating that putative mechanisms of action remain to be determined. Finally, VDR SNPs did not affect dietary intervention outcome in the present cohort.

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Fig. 1: The VDR gene on chromosome 12 and LD analysis.

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Funding

First author is supported by Indonesia Endowment Fund for Education (LPDP) scholarship. This study was supported by internal resources from Maastricht University. The funders had no role in the study design, data analysis, interpretation, and the preparation of this manuscript.

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Authors and Affiliations

  1. Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands

    A. Pramono, J. W. E. Jocken, W. H. M. Saris & E. E. Blaak

  2. Department of Nutrition Science, Faculty of Medicine, Diponegoro University, Semarang, Indonesia

    A. Pramono

  3. Maastricht Center for Systems Biology, Maastricht University, Maastricht, The Netherlands

    M. E. Adriaens

  4. Department of Nutrition, Exercise, and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark

    M. F. Hjorth & A. Astrup

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  1. A. Pramono
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Contributions

WHMS and AA designed the DiOGenes clinical study. AP, JWJ, and EEB designed the study. AP performed data analyses and wrote the manuscript. JWEJ and MEA supervised adipose tissue transcriptome data analysis. All authors contributed to revising the article critically and gave their final approval of the version to be published. EEB is the guarantor of this study.

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Correspondence to E. E. Blaak.

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Pramono, A., Jocken, J.W.E., Adriaens, M.E. et al. The association between vitamin D receptor polymorphisms and tissue-specific insulin resistance in human obesity. Int J Obes 45, 818–827 (2021). https://doi.org/10.1038/s41366-021-00744-2

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