CARDIOVASCULAR JOURNAL OF AFRICA • Vol 22, No 1, January/February 2011
AFRICA
25
Obesity-associated genetic variants in young Asian
Indians with the metabolic syndrome and myocardial
infarction
N RANJITH, RJ PEGORARO, R SHANMUGAM
Summary
Objective:
Associations between obesity-related polymor-
phisms and the metabolic syndrome in 485 young (
≤
45
years)Asian Indian patients with acute myocardial infarction
(AMI), and 300 matched controls were assessed.
Methods:
Genetic variants included the adiponectin 45T
→
G
and 276G
→
T, LEPR K109R and Q223R, MC4R-associated
C
→
T and FTOA
→
T polymorphisms.
Results:
The metabolic syndrome, as defined by NCEP ATP
III and IDF criteria, was diagnosed in 61 and 60% of patients,
respectively. No relationship was found between the obesity-
associated polymorphisms and the metabolic syndrome, or
between AMI patients and controls. The MC4R-associated
TT genotype occurred more frequently in patients with lower
triglyceride levels (
p
=
0.024), while the adiponectin 45 TT
genotype occurred more commonly in patients with normal
fasting glucose levels (
p
=
0.004). The LEPR Q223R TT geno-
type was associated with low high-density lipoprotein (HDL)
cholesterol levels (
p
=
0.003).
Conclusion:
The metabolic syndrome occurs commonly in
young Asian Indian patients with AMI. No relationship was
found between any obesity-associated polymorphism and the
metabolic syndrome. Particular genotypes may exert protec-
tive or disadvantageous effects on individual components of
the metabolic syndrome.
Keywords:
obesity, metabolic syndrome, myocardial infarction,
genetic polymorphisms
Submitted 18/1/10, accepted 14/3/10
Cardiovasc J Afr
2011;
22
: 25–30
DOI: CVJ-21.018
Obesity is recognised as a serious chronic disease, the preva-
lence of which is increasing worldwide. Several studies have
demonstrated a strong association between obesity and insulin
resistance. This relationship frequently leads to diabetes mellitus,
hypertension, dyslipidaemia and vascular inflammation, all of
which promote the development of atherosclerotic cardiovascu-
lar disease.
1-3
The co-occurrence of these metabolic risk factors
has given rise to the metabolic syndrome.
Although there are several definitions for the metabolic
syndrome, the National Cholesterol Education Program Adult
Treatment Panel III (NCEP ATP III)
4
and the International
Diabetes Federation (IDF)
5
definitions are the most widely used.
Fundamental to the syndrome is the close interaction between
abdominal fat patterning, total body adiposity, and insulin resist-
ance. Both definitions include central obesity as one of the
criteria, but with different waist circumference cut-offs. The IDF
definition of the metabolic syndrome, in fact, proposes central
obesity as an essential element, with specific waist circumfer-
ence thresholds set for different ethnic groups. In addition, the
metabolic syndrome is reportedly present in 60% of individuals
who are obese,
6
while an increased waist circumference, taken in
isolation, identifies up to 40% of individuals who will develop
the syndrome within five years.
7
Obesity is believed to be a heritable trait. However, the genes
that contribute to the less severe but more common forms of
obesity have been difficult to identify. Several studies have
demonstrated a possible role for the adiponectin gene in obesity,
insulin resistance and type 2 diabetes.
8-11
Adiponectin, which is
an adipocyte-derived cytokine, has been shown to be down regu-
lated in obesity, particularly in those individuals with visceral
obesity, while adiponectin levels correlate inversely with insulin
resistance.
12-14
Furthermore, preliminary data suggest that high
adiponectin concentrations are associated with a favourable
cardiovascular outcome.
15-16
It has been estimated that between
30 and 70% of the variability in adiponectin levels is determined
by genetic factors.
17
Although several polymorphisms in the
adiponectin gene have been described, data linking these variants
to obesity and related conditions are inconclusive.
Leptin is another important protein associated with obesity,
and functions by inhibiting food intake and stimulating energy
expenditure.
18
Leptin levels are regulated by various proteins, one
of which is the leptin receptor (LEPR). Several polymorphisms
are found in the LEPR gene but earlier studies, which examined
potential associations between LEPR gene polymorphisms and
obesity, failed to report conclusive results.
19,20
Nevertheless, both
the adiponectin and the LEPR genes remain potential candidates
in the aetiology of obesity and coronary heart disease (CHD).
Other genes have also been associated with obesity in the
general population, most notably the melanocortin-4-receptor
(MC4R) and the fat mass and obesity-associated (FTO) genes.
Activation of the MC4R gene reduces body fat stores by decreas-
ing food intake and increasing energy expenditure. Functional
mutations in the MC4R gene are reportedly associated with
hyperphagia, early-onset obesity and hyperinsulinaemia, while
polymorphisms near the MC4R gene are linked to increased
body mass index (BMI) and abdominal girth.
21,22
Variants in the
FTO gene have been associated with obesity in a genome-wide
study,
23
and have been shown to predispose to diabetes through
an effect on BMI.
24
Departments of Medicine, Coronary Care Unit, RK Khan
Hospital, Chemical Pathology, Nelson R Mandela School
of Medicine, University of KwaZulu-Natal, and Biostatistics
Unit, Medical Research Council of South Africa
NARESH RANJITH, MD, FESC,
ROSEMARY J PEGORARO, PhD
REBECCA SHANMUGAM, MSc
