Association of a genetic variant in the angiopoietin-like protein 4 gene with metabolic syndrome

Sara Kharazmi-Khorassani,Maryam Tayefi,Hamideh Ghazizadeh,Gordon A Ferns,Azam Rastegar-Moghadam,Jasmin Kharazmi-Khorassani,Amir Avan,Majid Ghayour-Mobarhan,Habibollah Esmaily,Sara Samadi

doi:10.1186/s12881-019-0825-8

Abstract

BackgroundMetabolic syndrome (MetS) is characterized by a clustering of cardiovascular risk factors that include: abdominal obesity, dyslipidemia, hypertension and glucose intolerance. Angiopoietin-like protein 4 (ANGPTL4) is a circulating peptide that is an inhibitor of lipoprotein lipase, a key enzyme in lipid metabolism. The objective of this study was to investigate the association of ANGPTL4 gene variants (E40K) with fasting serum triglyceride levels and with cardiovascular risk factors, that included the presence of MetS in 817 subjects recruited from the Mashhad stroke and heart Atherosclerosis Disorders (MASHAD) cohort Study.MethodANGPTL4 genotypes were determined using a TaqMan genotyping based real time PCR method. The association of the genetic variant with the risk of metabolic syndrome and its relationship with lipid profile were determined.ResultThe frequency of GG, GA and AA genotypes were 96.9, 2.7 and 0.4% in individuals with MetS, and 78.8, 20.8, 0.4%, in those without MetS. The GA genotype of the rs116843064 polymorphism was associated with a lower risk for MetS (e.g., OR in Codominant genetic model: 0.14, 95% CI: (0.06–0.33), p < 0.0001). Subject with an A allele had a higher risk for MetS (OR: 6.72, 95% CI: (3.05–14.82), p < 0.0001). There was a significant difference in fasted lipid profiles across the genotypes for ANGPTL4. Carriers of the AG genotype had higher levels of serum HDL-cholesterol (HDL-C) and lower TG, compared to the GG homozygotes genotype.ConclusionThe G allele at the rs116843064 polymorphic locus of the ANGPTL4 gene was associated with a lower prevalence of MetS.

Highlights

Metabolic syndrome (MetS) is characterized by a clustering of cardiovascular risk factors that include: abdominal obesity, dyslipidemia, hypertension and glucose intolerance
MetS was defined according to the International-Diabetes-Federation (IDF) criteria including waist circumference > 94 cm in men and > 80 cm in women along with at least two of the other criteria for MetS, such as fasting serum triglycerides> 150 mg/dl, High density lipoprotein (HDL)-C < 40 mg/dl in men or < 50 mg/dl in women, BP > 130/85 mmHg and fasting glucose> 100 mg/dl
Multiple studies have revealed that metabolic syndrome is a risk factor for diabetes mellitus, hypertension, pro-inflammatory state, central adiposity, dyslipidemia and high concentrations of Angiopoietin-like protein 4 (ANGPTL4) [18, 36]

Summary

Introduction

Metabolic syndrome (MetS) is characterized by a clustering of cardiovascular risk factors that include: abdominal obesity, dyslipidemia, hypertension and glucose intolerance. Angiopoietin-like protein 4 (ANGPTL4) is a circulating peptide that is an inhibitor of lipoprotein lipase, a key enzyme in lipid metabolism. Metabolic syndrome is increasing globally, and is important because of its association with increased cardiovascular disease (CVD) risk [1]. It affects about 20 to 25% of the adult population [2]. MetS is characterised by a clustering of CVD risk factors that include: high blood. Angiopoietin–like proteins 4 (ANGPTL4) is a circulating peptide which inhibits lipoprotein lipase [21] and

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