Journal of Current Biomedical Reports  jcbior.com 

Volume 1, Number 2, 2020                                                                                                          eISSN: 2717-1906 

1 

Original research 

Evaluation of the correlation between serum lipid characteristics 
of obese subjects and ADIPOQ gene rs266729 polymorphism in 

Chaharmahal and Bakhtiari Province of Iran 
 

Negar Rabiee1, Roohollah Nakhaei Sistani1, Ali Mohammad Ahadi2,*, Reza Baharloo3 
 

1 Department of Cellular and Molecular Biology, Faculty of Chemistry, Kashan University, Kashan, Iran 
2 Department of Genetics, Faculty of Science, Shahrekord University, Shahrekord, Iran 

3 Department of Medical Laboratory Sciences, Shahrekord University of Medical Sciences, Shahrekord, Iran 
 

Abstract 
Obesity is a multifactorial disorder that is influenced by various factors such as behavior, diet, 
environment, metabolic and genetic. This disease is the result of an imbalance between energy 
absorption and expenditure. Mutations in genes that are responsible for appetite control and 
metabolism are considered as the genetic component of obesity. Adiponectin protein is one of the most 
effective adipokines in regulating the body's energy homeostasis and fat storage, which is expressed by 
the ADIPOQ gene and secreted from white adipose tissue. The concentration of this protein in the blood 
decreases in obesity. In this study, the relationship between rs266729 (-11,377 C>G) polymorphism in 
the ADIPOQ gene with the level of biochemical parameters such as total cholesterol and triglyceride 
and HDL and LDL in the blood of obese people in Borujen (a city in Iran) was investigated. This study 
was performed on 100 people who referred to the Tamin Ejtemaee clinic due to obesity problems in 
Borujen. In this study, the ARMS-PCR method was used to determine the genotype of individuals. 
Based on the results of this study, no significant relationship was found between biochemical 
parameters including total cholesterol, triglyceride, and LDL with rs266729 polymorphism genotypes 
in ADIPOQ gene in obese subjects. We concluded that rs266729 polymorphism cannot be useful as an 
index parameter for predispose genotype for imbalance in total cholesterol, triglyceride, and LDL levels 
in a person. 

Keywords: Obesity, ADIPOQ gene, Cholesterol, Triglyceride 

 
1. Introduction 
Obesity is an epidemic disorder in the 21st 

century. According to epidemiological studies, the 
prevalence of overweight/obesity has been estimated 
to have increased by 41% from 1980 to 2013 (1,2). 
Obesity is an important issue for the public health 
organization because obesity and overweight increase 
the risk of several serious chronic diseases such as type 
2 diabetes, cardiovascular disease, hypertension and 

                                                           
* Corresponding author:  
Dr. Ali Mohammad Ahadi, Ph.D 
Department of Genetics, Faculty of Science,  
Shahrekord University, Shahrekord, Iran 
Tel/Fax: +98 38 32324419 
Email: Ahadi_al@sku.ac.ir 
https://orcid.org/0000-0001-9580-2740 
 
Received: September, 27, 2020 
Accepted: October, 23, 2020 

stroke, hypercholesterolemia, hypertriglyceridemia, 
osteoarthritis, asthma, and certain types of cancer (3). 
Obesity phenotype occurs when food intake constantly 
exceeds energy expenditure, resulting in a positive 
long-term energy imbalance (1). Overeating and 
decreased physical activity are two common causes of 
obesity, but in addition to them, decreased diversity of 
intestinal microflora, sleep deprivation, and endocrine 
disorders are also among the effective factors in 

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Rabiee et al.   

2 

increasing the prevalence of obesity (4). Scientists 
around the world have intensified their efforts to 
elucidate the pathophysiological mechanisms which 
lead to obesity or reinforce its main consequences, to 
create effective treatments for obesity and related 
disorders. In this process, the concept of 
adipocytokines has been defined and dysfunction of 
adipocytokine pathways has been identified as an 
important factor in obesity-related disorders. Also, the 
logical manipulation of adipocytokines is becoming a 
promising way to treat obesity and its metabolic 
abnormalities (5). 

Since adipokines regulate several important 
metabolic pathways, genetic variants that affect their 
function and efficiency may be involved in a variety of 
pathophysiological conditions. There is evidence that 
genetic variants in adipokine genes can modulate 
circulating adipokine levels, which can result in a 
specific metabolic change (e.g., obesity, insulin 
resistance, etc.). Therefore, a comprehensive analysis 
of genetic variants, including various and rare single 
nucleotide polymorphisms, may provide new insights 
into the specific role of studied adipokines in the 
pathophysiology of metabolic diseases (6). 

Adiponectin is an adipokine that is mainly 
secreted from adipocytes (7,8) and its expression is 
reduced in obesity (9). Human adiponectin is encoded 
by the ADIPOQ gene with the access number of 
NM_001177800 for mRNA in the NCBI Genomic 
Database. This gene is located at chromosomal locus 
3q27 (chromosomal locus NC_000003.12) (5,10,11). 
Circulating adiponectin may act as a biomarker, and 
its decreased circulating levels may play a mediating 
role in the pathophysiology of type 2 diabetes, 
metabolic syndrome, obesity, and atherosclerosis 
(7,12). This plasma protein increases fatty acids 
oxidation and reduces circulating fatty acids 
concentration (13). 

Regarding the effect of adiponectin on lipid 
metabolism, adiponectin may increase HDLc levels. 
Also, adiponectin can inhibit the catabolism of 
triglyceride-rich lipoproteins, and consequently 
lowering triglyceride levels (14). However, in one 
meta-analysis, no association was reported between 
adiponectin gene polymorphisms and lipids (15). In 
general, adiponectin is negatively correlated with 
HDLc and positively correlated with LDLc and 
triglyceride concentrations (16). A positive correlation 
has also been reported between adiponectin and 

lipoprotein lipase (17). A similar association has been 
reported between adiponectin, HDLc, and triglyceride 
in adolescent and postmenopausal women (18). Even 
in the elderly, adiponectin is positively associated with 
HDLc and the TC/LDLc ratio (19). However, in 
patients with type 2 diabetes mellitus (T2DM), 
conflicting results have been reported due to the 
association between adiponectin, HDLc, and 
triglycerides (20,21). HDL dysfunction may be 
involved in increasing the risk of cardiovascular 
disease (CVD). Adiponectin is involved in increasing 
HDL particle size and thus improves HDL quality (22). 

Due to the contradictory results observed in the 
effect of adiponectin gene on the level of serum lipid 
profiles in obese and other metabolic diseases, in this 
study, we aimed to investigate the correlation between 
rs266729 polymorphism of the adiponectin gene and 
the level of serum lipid characteristics of obese 
individuals in Southwest of Iran. 

 
2. Materials and methods 
2.1 Patients and control group 
Participants in this study were selected based on 

the criteria defined in the World Health Organization 
for obesity. Therefore, subjects with BMI≥30 were 
included in our study. Participants did not have 
underlying diseases, like diabetes. The study protocol 
was approved by the ethics committee of the Kashan 
University of Science according to the Declaration of 
Helsinki and written informed consent was obtained 
from each subject. 

 
2.2 Sampling and measurement of biochemical 

characteristics 
In this study, blood samples were taken from 100 

individuals who had referred to the Tamin Ejtemaee 
Clinic, Borujen, Charmahal Va Bakhtiari province, 
Iran, due to the obesity problem. Biochemical 
parameters such as total cholesterol, triglyceride, 
HDL, and LDL levels were measured by an 
autoanalyzer (Alpha-6-ISFAHAN SANJESH 
Equipment Company, Iran). 

 
2.3 DNA extraction and genotyping 
DNA extraction was performed by the phenol-

chloroform method from whole blood samples and the 
ARMS-PCR method was used to determine the 
genotype of individuals. This method is a specific 
allelic PCR for wild type and mutant sequences that 



Rabiee et al.   

3 

use specific primers. In the ARMS-PCR method, two 
complementary reactions are performed for the 
detection of each allele in polymorphism. One of the 
reactions involves a specific primer for the mutant 
allele and the other contains a specific primer for the 
wild type allele (23). This method is one of the most 
suitable methods for detecting known mutations and 
is based on the 3  ́ end nucleotide of the primers. In 
other words, if this nucleotide is the complementary 
base of the target base, a PCR product would be 
obtained, otherwise, the product would not be seen in 
the gel, and a product for a primer that its 3  ́ end 
complementary of another allele must be detected. If 
PCR products are present in both cases, the person 
would be heterozygous. The absence of the product in 
both cases of primers indicates a technical problem in 
PCR and the lack of optimal conditions. Many studies 
can be mentioned regarding the application of the 
ARMS technique. Also, a comparison of the 
advantages of this technique has been considered in 
some researches and its applicability in molecular 
detection has been proven (24–26). To perform this 
technique, 4 primers were designed using Gene 
runner software (version 6.5.51 Beta) including two 
specific primers for the detection of wild type and 
mutated alleles and two other primers for both sides of 
the amplicon. The names and sequences of the 
primers are given in Table 1. In this study, the final 
volume of the reaction mixture in each microtube was 
considered to be 25 μl and a separate PCR reaction was 
used to identify each of the C and G alleles. The 
amount of substances used in each of the reactions was 
as follows: the concentration of substances used to 
detect the G allele; PCR 1X buffer, magnesium chloride 
1.5 mM, dNTP 200 µM, forward primer 0.4 µM, 
reverse primer specific for G allele 0.4 µM, template 
DNA 0.1-1 µg/ml, Taq DNA polymerase 1 U (Sinagen 
Company, Iran), the concentration of substances in 
the PCR reaction for detection of the C allele is the 
same. The PCR reaction was started with initial 
denaturation for 5 minutes at 94 °C and followed by 35 
cycles of 3 steps consisted of denaturation at 94 ° C for 
30 seconds, annealing at 55 for the G allele, and at 58 ° 
C for the C allele for 40 seconds and elongation step at 
72 ° C for 30 seconds. Finally, the final extension was 
performed at 72 ° C for 5 minutes. After the ARMS-
PCR reaction, the samples were run on 2% agarose gel. 
ARMS-PCR product length was 115 bp for G allele and 
211 bp for C allele identification.  

2.4 Statistical analysis 
In this study, SPSS ver. 26 software (IBM Corp., 

USA) was used for statistical analysis. Kolmogorov-
Smirnov test was used to calculate the normality of 
data distribution and the ANOVA parametric test was 
utilized to calculate the significance of data with 
normal distribution and the Kruskal-Wallis non-
parametric test was used for data with a normal 
distribution. Tukey and LSD tests were also employed 
to evaluate the significant relationship between 
biochemical characteristics and each of the 
polymorphism genotypes. In all tests, a P value of less 
than 0.05 showed a significant difference between the 
two groups.  

 

 
3. Results 
Demographic information and mean serum lipid 

profile levels of obese individuals are listed in Table 2. 
Data normality was assessed using the Kolmogorov-
Smirnov test. HDL and LDL indices had a normal 
distribution and total cholesterol and triglyceride 
indices had abnormal distribution. Therefore ANOVA 
test was used to evaluate the significant relationship 
between HDL and LDL indices and the Kruskal-Wallis 
test was utilized to evaluate the total cholesterol and 
triglyceride indices (Table 3). According to Table 3, no 
significant correlation was found between biochemical 
characteristics consisted of the levels of cholesterol (P 
= 0.182), triglyceride (P = 0.431), HDL (P = 0.451) and 
LDL (P = 0.188) and CC, CG and GG genotypes of 
ADIPOQ rs266729 polymorphism. 

In this study, the collected data were analyzed by 
Tukey and LSD methods. These two methods focus on 
comparing means, while ANOVA and Kruskal-Wallis 
tests focus on the variance of the whole data. Tables 4 
and 5 show the results of Tukey and LSD tests for 
rs266729 polymorphism. According to the results of 
these    tests,    no    significant    correlation    was    found 

 

 Table 1. Names and sequences of primers 

 

Name Sequence 

FNRA377 5ʹ-CCTTTCTCACCCTTCTCACC-3ʹ 

RNRB377 5ʹ-CGCCCATGTTTTGTTTTTGAAGC-3ʹ 

FNRC377 5ʹ- GAACCGACTCAGATCCTGCC-3ʹ 

RNRD377 5ʹ- GCCTGGAGAACTGGAAGCTG -3ʹ 

 
 



Rabiee et al.   

4 

between any of the CC, CG, GG genotypes of ADIPOQ 
rs266729 polymorphism, and biochemical 
characteristics including total cholesterol, triglyceride, 
HDL, and LDL levels in obese subjects. 
 

Table 2. Mean parameters measured in obese 

subjects 

 

Parameter 
Obese subjects 

Mean ± SD 

Gender (Male/Female) 52/48 

Age (year) 50.19 ± 13.42 

BMI (kg/m2) 39.77 ± 5.03 

Total cholesterol (mg/dl) 236.05 ± 31.55 

Triglyceride (mg/dl) 238.96 ± 99.68 

HDL (mg/dl) 41.57 ± 11.85 

LDL (mg/dl) 146.55 ± 31.18 

 

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Rabiee et al.   

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4. Discussion 
The role of the ADIPOQ gene in controlling the 

metabolism of lipids and carbohydrates has been 
confirmed in many studies (7,27). In the present study, 
we focused on a polymorphism that could play a role 
in gene expression. The involvement of this 
polymorphism in related metabolic disorders has been 
reported in several studies (28–30). 

High triglyceride levels and low high-density 
lipoprotein (HDL) cholesterol levels are of features of 
the metabolic syndrome which is one of the metabolic 
syndrome hallmarks of obesity. Elevated levels of 
small, dense, low-density lipoprotein (LDL) 
cholesterol particles in plasma are key features 
associated with high triglyceride and low HDL 
cholesterol levels in people disposed to gain weight. 
Accumulation of dense small LDL particles also 
increases in subjects with abdominal fat accumulation 
(large waist circumference). In the mechanism of 
excessive accumulation of intra-abdominal (visceral) 
fat, elevated levels of total cholesterol and LDL 
cholesterol, although common, are mainly associated 
with the consumption of saturated fats, and are not 
necessarily associated with weight gain and obesity 
(31). 

The importance of parameters including 
triglycerides, HDL, LDL, and total cholesterol in 
relation to obesity has been considered in many 
studies. For example, Feingold and Granfeld reported 
that 60 to 70 percent of obese people show blood lipids 
disturbances, which can indicate LDL, HDL, or 
triglyceride levels outside the normal range in the 
blood (32). A study in the Chinese population 
examined the correlation between HDLc levels and 
obesity and found a negative association between 
blood HDLc levels and obesity (33). Klopp et al. 
demonstrated that obesity increases the risk of 
cardiovascular disease due to some risk factors such as 
elevated triglyceride levels, elevated LDL levels, and 
decreased HDLc levels (34). Dastani et al. showed 
convincing evidence of an association between several 
adiponectin-lowering genes and SNP with decreased 
body mass index (BMI), increased waist-to-hip ratio 
(WHR), high triglyceride (TG) levels, and low HDL 
levels (35). Interestingly, in a study of two variants in 
the ADIPOQ gene promoter, -11391 G>A and -11377 
C>G were associated with abdominal obesity, TG 
levels, and an increased risk of metabolic syndrome in 
the young population aged 20-33 years (36). For the 

first time, a study by Kaftan and Hussein showed an 
inverse relationship between HDL levels and 
rs266729 polymorphism in the Iraqi population. This 
was the first study in which such a relationship has 
been reported (37). Sun et al. (2008) examined this 
relationship and found no correlation between 
circulating HDL levels and rs266729 polymorphism in 
the Chinese population (38), which confirms the 
results of our study. This study shows that especially 
when performing genetic analysis, the origin of the 
subjects should be carefully considered and because 
the genetic variants do not necessarily follow the same 
pattern among the different populations, the origin of 
study subjects should be considered. In our results and 
Tukey and LSD tests, according to Tables 4 and 5 for 
rs266729 polymorphism, no significant correlation 
was found between the genotypes of rs266729 
polymorphism and biochemical characteristics of 
obese individuals. The lack of significant differences in 
the levels of biochemical parameters among the 
participants indicates accurate sampling, in other 
words, the lack of specific differences for some reasons 
such as hormonal diseases or environmental factors in 
the cause of obesity, for the inclusion of individuals in 
the study. The variant of rs266729 polymorphism 
does not show a significant relationship with these 
characteristics; it can be due to the lack of effect of 
these variants on changes in adiponectin levels, or the 
adiponectin level defect may be compensated by other 
molecules through alternative pathways (39,40). 
Finally, it should be considered that unstudied 
polymorphisms involved in the imbalance of 
association with the genetic variants of adiponectin 
may also play a role in changes in plasma levels of 
adiponectin (6). 

One of the limitations of our study was the 
number of samples. In addition, the relationship 
between -11,377 C>G adiponectin gene polymorphism 
and serum lipid characteristics level of obese subjects 
needs to be investigated in other populations, also 
other polymorphisms of adiponectin gene need to be 
considered. 

Our study showed that there is no significant 
correlation between biochemical parameters 
including total cholesterol, triglycerides, HDL, and 
LDL levels with ADIPOQ rs266729 polymorphism. 
Also, according to the results of our study no 
significant association between different genotypes of 
this polymorphism in obese individuals with serum 



Rabiee et al.   

6 

levels of total cholesterol, triglyceride, HDL, and LDL 
was observed. The lack of relevance of these 
characteristics can be related to their multifactorial 
nature, such as diet and nutrition. 

 
Acknowledgements 
We thanks Kashan University and Shahrekord 

University for their supports. Also we thanks Tamin 
Ejtemaee Clinic, Borujen, Charmahal Va Bakhtiari 
province of Iran. 

 
Author Contributions 
Laboratory work has done by NR as her MSc 

thesis, also, collaborated in writing. AMA participated 
as the group leader and the owner of the idea and the 
main author of the article. RN was collaborated as 
supervisor of thesis in Kashan University. RB was 
collaborate as advisor of this thesis and sampling and 
management of participants in this study. All authors 
read and approved the final version of manuscript. 

 
Conflict of Interests 
The authors declare that they have no competing 

interests. 
 
Ethical declarations 
The study has been approved by the ethical 

committee of Kashan University of Sciences. 
 
Financial Support 
Research Director of Kashan University financials 

for MSc thesis. 
 
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