Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

ANGPTL3 Variants Associate with Lower Levels of Irisin and C-Peptide in a Cohort of Arab Individuals

Muath Alanbaei
ORCID logo ,
Mohamed Abu-Farha
ORCID logo ,
Prashantha Hebbar
,
Motasem Melhem
,
Betty S Chandy
,
Emil Anoop
,
Preethi Cherian
,
Irina Al Khairi
,
Fadi Alkayal
,
Fahd Al-Mulla
* ORCID logo ,
Jehad Abubaker
* ,
Thangavel Alphonse Thanaraj
*
Version 1 : Received: 11 May 2021 / Approved: 12 May 2021 / Online: 12 May 2021 (07:28:31 CEST)

A peer-reviewed article of this Preprint also exists.

Alanbaei, M.; Abu-Farha, M.; Hebbar, P.; Melhem, M.; Chandy, B.S.; Anoop, E.; Cherian, P.; Al-Khairi, I.; Alkayal, F.; Al-Mulla, F.; Abubaker, J.; Thanaraj, T.A. ANGPTL3 Variants Associate with Lower Levels of Irisin and C-Peptide in a Cohort of Arab Individuals. Genes 2021, 12, 755. Alanbaei, M.; Abu-Farha, M.; Hebbar, P.; Melhem, M.; Chandy, B.S.; Anoop, E.; Cherian, P.; Al-Khairi, I.; Alkayal, F.; Al-Mulla, F.; Abubaker, J.; Thanaraj, T.A. ANGPTL3 Variants Associate with Lower Levels of Irisin and C-Peptide in a Cohort of Arab Individuals. Genes 2021, 12, 755.

Abstract

ANGPTL3 is an important regulator of lipid metabolism. Its inhibition in people with hypercholesteremia reduces plasma lipid levels dramatically. Genome-wide association studies have associated ANGPTL3 variants with lipid traits. Irisin, an exercise modulated protein, has been associated with lipid metabolism. Intracellular accumulation of lipids impairs insulin action and contributes to metabolic disorders. In this study, we evaluate the impact of ANGPTL3 variants on levels of irisin and markers associated with lipid metabolism and insulin resistance. ANGPTL3 rs1748197 and rs12130333 variants were genotyped in a cohort of 278 Arab individuals from Kuwait. Levels of irisin and other metabolic markers were measured by ELISA. Significance of association signals was assessed using Bonferroni-corrected P-values and empirical P-values. The study variants were significantly associated with low levels of c-peptide and irisin. Levels of c-peptide and irisin were mediated by interaction between carrier genotypes (GA+AA) at rs1748197 and measures of IL13 and TG, respectively. While levels of c-peptide and IL13 were directly correlated in individuals with reference genotype, they were inversely correlated in individuals with carrier genotype. Irisin correlated positively with TG which is strong in individuals with carrier genotypes. These observations illustrate ANGPTL3 as a potential link connecting lipid metabolism, insulin resistance and cardioprotection.

Keywords

ANGPTL3-DOCK7; irisin; c-peptide; triglyceride; interleukin 13; lipid metabolism; insulin resistance; Arab population

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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