Abstract
BackgroundMechanisms involved in metabolic syndrome (MetS) development include insulin resistance, weight regulation, inflammation and lipid metabolism. Aim of this study is to investigate the association of single nucleotide polymorphisms (SNPs) involved in these mechanisms with MetS.MethodsIn a random sample of the EPIC-NL study (n = 1886), 38 SNPs associated with waist circumference, insulin resistance, triglycerides, HDL cholesterol and inflammation in genome wide association studies (GWAS) were selected from the 50K IBC array and one additional SNP was measured with KASPar chemistry. The five groups of SNPs, each belonging to one of the metabolic endpoints mentioned above, were associated with MetS and MetS-score using Goeman’s global test. For groups of SNPs significantly associated with the presence of MetS or MetS-score, further analyses were conducted.ResultsThe group of waist circumference SNPs was associated with waist circumference (P=0.03) and presence of MetS (P=0.03). Furthermore, the group of SNPs related to insulin resistance was associated with MetS score (P<0.01), HDL cholesterol (P<0.01), triglycerides (P<0.01) and HbA1C (P=0.04). Subsequent analyses showed that MC4R rs17782312, involved in weight regulation, and IRS1 rs2943634, related to insulin resistance were associated with MetS (OR 1.16, 95%CI 1.02-1.32 and OR 0.88, 95% CI 0.79; 0.97, respectively). The groups of inflammation and lipid SNPs were neither associated with presence of MetS nor with MetS score.ConclusionsIn this study we found support for the hypothesis that weight regulation and insulin metabolism are involved in MetS development.MC4R rs17782312 and IRS1 rs2943634 may explain part of the genetic variation in MetS.
Highlights
Mechanisms involved in metabolic syndrome (MetS) development include insulin resistance, weight regulation, inflammation and lipid metabolism
In a recent genome-wide association study (GWAS) even all single nucleotide polymorphisms (SNPs) associated with MetS were involved in lipid metabolism [5]
The group of abdominal obesity SNPs was significantly associated with waist circumference (P=0.01), the group of insulin resistance SNP with haemoglobin A1c (HbA1C) (P=0.04) and the group of inflammation SNPs with High sensitive C-reactive protein (hsCRP) (P=7.3*10-6)
Summary
Mechanisms involved in metabolic syndrome (MetS) development include insulin resistance, weight regulation, inflammation and lipid metabolism. Aim of this study is to investigate the association of single nucleotide polymorphisms (SNPs) involved in these mechanisms with MetS. The metabolic syndrome (MetS) is a common multicomponent condition consisting of abdominal obesity, dyslipidaemia, hypertension and hyperglycaemia. It is associated with an increased risk of CVD (cardiovascular diseases) and T2D(type 2 diabetes) [1]. Several mechanisms, including insulin resistance [1], abdominal obesity [1], and inflammation [2,3] have been proposed to underlie the clustering of MetS features. In a recent genome-wide association study (GWAS) even all single nucleotide polymorphisms (SNPs) associated with MetS were involved in lipid metabolism [5]. If effect sizes of SNPs involved in weight regulation and insulin resistance, pathways for which strong pathophysiological evidence exists [1], are small, these SNPs would not have been detected in GWAS, which have a low power due to adjustment for the large number of associations tested
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