Elsevier

Gene

Volume 561, Issue 1, 25 April 2015, Pages 1-5
Gene

Association of RBP4 gene variants with adverse lipid profile and obesity

https://doi.org/10.1016/j.gene.2014.12.071Get rights and content

Highlights

  • All the features between obese and non-obese subjects were significantly different.

  • In rs3758539, minor allele carriers in cases were significantly higher than in controls.

  • In cases, weight, waist.c, HDL, LDL, and rs10882280 were risk factors of obesity.

  • In controls, sex, age, weight, FBS, and rs3758539 were risk factors of obesity.

Abstract

Obesity is currently a worldwide public health problem. Retinol-binding protein4 (RBP4) is a recently discovered adipokine, which is potentially associated with insulin resistance and obesity. We aimed to investigate whether genetic variation within the RBP4 gene is correlated with the obesity and lipid profile in Iranian population. 321 samples were randomly selected from participants of Isfahan Healthy Heart Program (IHHP). Genomic DNA was isolated from peripheral blood cells (PBCs) and HRM-PCR was performed in order to investigate the presence of SNPs, and further sequencing analysis was done from selected subjects according to the differences of HRM curve pattern. Statistical analyses were performed using SPSS v16.00. The difference of the presence of rs3758539 polymorphism between controls and obese patients was significant, but not about rs10882280. We found noticeable association among genetic polymorphisms and biomedical and physical characteristics within investigated population. Our findings suggested that variations in the RBP4 gene were correlated with BMI and polymorphisms more likely could contribute to the development of obesity in our population. Also appraisal of obesity risk factors within each group might be helpful for preventing obesity initiation and could have a possible role in a predisposition to obesity in the Iranians.

Introduction

Obesity is currently a worldwide public health problem (Kelishadi, 2007). Increasing burden of obesity leads to increased morbidity and mortality due to metabolic syndrome, insulin resistance, type-2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) (Mensah et al., 2004). There is a progressive increase in obesity in both children and adolescent groups in the last decade in Iran (Sarrafzadegan et al., 2010).

The underlying mechanism of obesity is very complex, including interactions among behavioral, environmental, and genetic factors. Increasing prevalence of obesity can be attributed to highly calorific food intake and relatively sedentary lifestyle of modern times. Several studies have shown important role of genetic components in the risk of becoming obese (Lyon and Hirschhorn, 2005, Xia and Grant, 2013). Retinol-binding protein4 (RBP4) is a recently discovered adipokine that belongs to the lipocalin family of proteins, which is potentially in association with insulin resistance (Yang et al., 2005). RBP4 is released from the liver as a primary source, and also from the adipose tissue as the alternate source (Tsutsumi et al., 1992). RBP4 acts as a carrier protein for retinol (one of the animal form of vitamin A), and other small hydrophobic molecules (Newcomer and Ong, 2000). Overexpression of RBP4 in visceral adipose tissue would cause elevated level of serum RBP4 and consequently leads to the accumulation of visceral fat and causes insulin resistance (Kloting et al., 2007). Although, the association between RBP4 and level of insulin (Kovacs et al., 2007) and insulin sensitiveness (Craig et al., 2007) was reported in previous researches, further studies couldn't find a significant association (Hu et al., 2008).

Serum RBP4 levels are associated with body mass index (BMI) in diabetic or non-diabetic obese patients (Yang et al., 2005, Graham et al., 2006). There are several RBP4 gene variants that are related to the adiposity level and adipose tissue accumulation (Kotnik et al., 2011). The RBP4 maps to chromosome 10q23–q24 in humans, closely to a region that has been linked with increased risk for type-2 diabetes in other populations (Ping et al., 2012).

Since pivotal role of RBP4 gene in obesity progresses, we therefore aimed to investigate whether genetic variation within the RBP4 gene correlates with the obesity in participants of Isfahan Healthy Heart Program (IHHP). We screened the RBP4 gene for 2 specific sequence variants rs3758539 and rs10882273 that have been previously linked with the development of T2DM and obesity in humans (Craig et al., 2007, Kovacs et al., 2007) and hypothesized that variations of these SNPs are associated with Iranian obese subjects.

Section snippets

Patients and setting

This project was conducted as a sub-study of the Isfahan Healthy Heart Program (IHHP), which is a comprehensive action-oriented integrated community-based intervention program for the prevention and control of non-communicable diseases (NCDs), which was implemented in central Iran. For the current study, we randomly selected 321 samples from participants of IHHP with the age range of 19 to 60 years. The participants were divided in 2 subgroups according to the body mass index (BMI) including 129

Results

In the present study, the relationship among rs3758539 and rs10882280 SNPs and level of various factors of investigated subjects were performed. Demographic characteristic of all participants is demonstrated in Table 2. The summary of SNP description with minor allele frequency is shown in Table 3. Table 4 provided the allele frequencies and also genotype profile of studied population. As demonstrated in Table 4, there was a significant association between G allele and A allele in rs3758539

Discussion

Many studies have reported the impact of genetic variations of RBP4 gene on BMI and obesity. The results of the present study have shown the association between variants in RBP4 gene and BMI level in our population. Although in rs3758539 we found the significant direct proportions of BMI mean level with minor allele frequency in the case group, in the control group minor allele had reverse effect on BMI mean level.

In the current study in agreement with the previous investigation, it has been

Conflicts of interest statement

The authors have declared no conflicts of interest.

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