CARDIOVASCULAR JOURNAL OF AFRICA • Vol 22, No 1, January/February 2011
28
AFRICA
phisms studied here and the clinical and biochemical compo-
nents of the metabolic syndrome was assessed. Significant asso-
ciations are shown in Table 4. The TT genotype of the MC4R-
associated polymorphism was found more frequently in patients
with lower triglyceride levels (OR 1.55; 95% CI 1.05–2.28;
p
=
0.024), while the major TT genotype of the adiponectin 45T
→
G
polymorphism occurred significantly more frequently in patients
with normal fasting blood glucose levels (OR 1.92; 95% CI
1.21–3.09;
p
=
0.004). The TT genotype of the LEPR Q223R
polymorphism was associated with low HDL cholesterol levels
(OR 2.35; 95% CI 1.28–4.52;
p
=
0.003).
A possible synergistic relationship between the six polymor-
phisms studied and the metabolic syndrome was analysed by
counting the number of variant alleles carried by each individual.
No relationship was observed between the cumulative polymor-
phic load and the metabolic syndrome by either definition, or the
control subjects.
Discussion
The metabolic syndrome is a common finding in young South
African Indians with AMI, irrespective of the definitive criteria
used (61% for NCEP ATP III and 60% for IDF). Male subjects
were in the majority, but proportionally more females were found
to have the metabolic syndrome (
p
=
0.007 and 0.02 for NCEP
ATP III and IDF, respectively). These results are in agreement
with previous studies, which reported a greater prevalence of the
metabolic syndrome in women compared with men.
28,29
Another interesting observation in our young patients was
the increased prevalence of visceral obesity with the metabolic
syndrome, as assessed by waist circumference measurements.
Although only 19% of subjects in this study cohort were
considered to be obese based on BMI measurements, it has
been reported recently in South Asians that the risk level for the
development of an adverse metabolic profile, with respect to
body fat, is reached at a much lower BMI (21 kg/m
2
) compared
to Europeans (
≥
30 kg/m
2
).
30
Furthermore, the predominance of
visceral adipose tissue with increasing waist circumference in
Asian Indians
31
has been shown to be associated with a higher
prevalence of the metabolic syndrome, compared with African–
Americans in whom subcutaneous fat predominates.
32
Therefore the higher frequency of obesity and the metabolic
syndrome in the South African Asian Indian patients in this study
may explain in part the accelerated onset of atherosclerotic
disease in these subjects compared to other ethnic groups. This
concurs with other studies on CHD in Asian Indians, in whom
about half of all myocardial infarctions occured in individuals
under the age of 50, with 25% being under 40 years of age.
33
With respect to the polymorphic variants in the adiponectin,
LEPR, MC4R and FTO genes, no significant differences in
allele frequency or genotype distribution were observed between
patients with the metabolic syndrome, irrespective of the defini-
tion used, compared to those who did not have the syndrome.
A previous study by Filippi
et al
.
34
demonstrated a significant
association between the adiponectin 276G
→
T polymorphism
and the early onset of CHD. No similar relationship was found in
our young patients with AMI for either the adiponectin 45T
→
G
or 276G
→
T polymorphisms, which agrees with the findings of
Jung
et al.
in their Korean subjects.
35
Given the complexity of the metabolic syndrome and the
lack of clarity surrounding its definition, most reports to date
have been restricted to the examination of the relationship
between variant polymorphisms and the individual criteria
of the metabolic syndrome, rather than with the syndrome as
a whole. For example, individuals carrying the adiponectin
276G
→
T polymorphism were found to be associated with type
2 diabetes mellitus in the Japanese population.
36
In European
subjects, conflicting results have been reported on the relation-
ship between the LEPR Q223R polymorphism and obesity.
37,38
Common polymorphisms in the MC4R and the FTO genes have,
however, been shown to be predictive of obesity and diabetes.
39
In the current study, the TT genotype of the adiponectin
45T
→
G gene occurred more frequently in patients with normal
fasting blood glucose levels (
p
=
0.004), suggesting a protec-
tive influence of the major allele, while the TT genotype of the
MC4R-associated polymorphism was found more frequently in
patients with low triglyceride levels (
p
=
0.024). In contrast, the
TT genotype of the LEPR Q223R polymorphism was strongly
associated with low HDL cholesterol levels (
p
=
0.003). To the
best of our knowledge, this is the first time that these findings
have been reported in the Asian Indian population, and clearly
warrant further evaluation in larger studies of different ethnic
backgrounds. No other associations were found for any of the
other polymorphic variants examined with any individual crite-
ria of the NCEP ATP III and IDF definitions of the metabolic
syndrome, including obesity.
Several limitations of this study merit consideration. Serum
adiponectin and leptin levels were not measured, and therefore
the functional significance of the polymorphisms studied cannot
be assessed. Previous findings on the association between
adiponectin polymorphisms and serum adiponectin levels have
been contradictory,
40,41
suggesting that serum levels may not
necessarily reflect the overall amount of adiponectin in the
body or its concentration in the interstitial space. With respect
TABLE 4. ASSOCIATION BETWEEN OBESITY-RELATED
POLYMORPHISMSAND INDIVIDUAL CRITERIA OF
THE METABOLIC SYNDROME
Triglycerides
<
1.7
Triglycerides
≥
1.7
Genotype
n
(%)
n
(%)
OR (95%CI)
p
-value
MC4R (rs17882313)
CC
21 (12)
40 (13)
0.85 (0.46–1.55) 0.672
TC
65 (36)
135 (45)
0.69 (0.46–1.02) 0.056
TT
95 (53)
125 (42)
1.55 (0.105–2.28) 0.024*
Glucose
<
5.6 Glucose
≥
5.6
Adiponectin 45 T
→
G
TT
128 (79)
212 (66)
1.92 (1.21–3.09) 0.004*
TG
31 (19)
99 (31)
0.53 (0.32–0.85) 0.006*
GG
3 (2)
9 (3)
0.65 (0.11–2.66) 0.740
HDL
(males
<
1.03)
(females
<
1.29)
HDL
(males
>
1.03)
(females
>
1.29)
LEPR Q223R
TT
68 (22)
16 (11)
2.35 (1.28–4.52) 0.003*
TC
134 (44)
81 (55)
0.64 (0.42–0.97) 0.027
CC
101 (33)
49 (34)
0.99 (0.64–1.54) 1.000
*Implies significance at the 5% level of significance.
Glucose: fasting blood glucose levels, MC4R: melanocortin-4-receptor,
LEPR: leptin receptor, HDL: high-density lipoprotein.
