Common Sequence Variants in CD163 Gene are Associated with Plasma Triglyceride and Total Cholesterol Levels in Severely Obese Individuals

Guénard F Cormier M,Tchernof A Deshaies Y,Biron S Lescelleur O

doi:10.4172/2161-1017.1000146

Abstract

Objective: The CD163 glycoprotein is a member of the scavenger receptor cysteine-rich superfamily acting as an inflammatory modulator inducing anti-inflammatory pathways. Previous findings from our group identified this gene as being differentially expressed in visceral adipose tissue (VAT) of severely obese men with vs. without the metabolic syndrome. The current study aimed to test the association between CD163 gene polymorphisms and obesity-related metabolic complications. Methods: Sequencing of the CD163 gene region was conducted in 25 severely obese individuals. Eleven tagging SNPs (tSNP) were selected and tested for association with obesity-related complications in nearly 1900 severely obese individuals. To further explore potential mechanisms underlying associations identified, the impact of tSNPs on methylation levels of 3 CpG sites (two promoter and one intronic) and gene expression levels were tested in a subset of 14 individuals. Results: Rare allele carriers for rs7980201 demonstrated lower fasting total cholesterol (total-C) levels (p=0.01) while rs4883263 rare allele carriers had increased total-C (p=0.04) and triglyceride (TG) levels (p=0.01). An association identified between rs7980201 SNP and methylation level of a promoter CpG site (p=0.04) suggested an impact on CD163 gene methylation in VAT, but such association was not reflected at gene expression level. Conclusion: The current study reports association of CD136 gene variations with fasting total-C and TG levels and suggests that CD163 SNPs could contribute to the inter-individual variability observed in obesity-related metabolic complications.

Highlights

Obesity increases the risk for several chronic diseases including cardiovascular diseases (CVD) and type 2 diabetes mellitus (T2DM) [1]
Not listed at the time, the CD163 gene was among the list of 489 differentially expressed genes and significantly overexpressed (1.6-fold; p = 0.02) in visceral adipose tissue (VAT) of metabolic syndrome (MetS)+ vs. MetS- obese men
The CD163 gene was found to be overexpressed in VAT of MetS+ obese men according to RT-PCR results (MFED = 1.51; p=0.03)

Summary

Introduction

Obesity increases the risk for several chronic diseases including cardiovascular diseases (CVD) and type 2 diabetes mellitus (T2DM) [1]. Excess accumulation of fat inside the abdominal cavity (visceral adipose tissue: VAT) is associated with altered insulin sensitivity, blood pressure (BP), and plasma lipid profile [2,3]. The clustering of many CVD risk factors including accumulation of abdominal fat, impaired glucose tolerance, dyslipidemia, and hypertension defines the metabolic syndrome (MetS) [4]. Increased circulating levels of inflammatory markers have been reported in obesity [5] concomitant to immune cell infiltration and activation in white adipose tissue [6] and have been identified as independent risk factors for CVD [7]. The severely obese population is heterogeneous regarding CVD risk profile [10] and the pathogenesis of the MetS and its components in subgroups of obese individuals likely involves multiple interactions among behavioral, environmental, and genetic factors [11,12]. A previous transcriptomic study from our group comparing gene expression profile in VAT of non-diabetic obese men with the MetS (MetS+) vs. obese men without the MetS (MetS-) [16]

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Discussion

Conclusion