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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 27, No 4, July/August 2016
AFRICA
215
Discussion
Indian populations throughout the world show early-onset CAD,
one to two decades earlier than other ethnic groups.
13
South
African Indians have the highest mortality rates due to CAD, while
black South Africans have a very low prevalence of the disease.
10
Increasing evidence has shown that SIRT1 is involved in
CAD by regulating a number of key metabolic and physiological
processes. SIRT1 serves as an anti-atherosclerotic factor
by mediating endothelial nitric oxide synthase (eNOS) and
improving endothelial dysfunction, regulating inflammation,
reversing cholesterol transport and reducing the risk of CAD.
14
Several SNPs have been identified in SIRT1, a candidate
molecule involved in the epigenetic regulation of CAD. To date,
there are only a few human genetic association studies regarding
SIRT1 SNPs and CAD. Our study was the first investigation of
SIRT1 rs1467568
and
rs7895833
in SA Indian CAD patients. We
observed that the variant alleles of both SIRT1 SNPs occurred
more frequently in SA Indians compared to SA blacks. We did
not observe any difference in allele frequencies between CAD
patients and control groups.
Previous studies have shown that some of the SIRT1 SNPs are
associated with BMI and obesity, glucose tolerance and diabetes,
blood pressure, cholesterol metabolism and coronary artery
calcification, all of which contribute to the CAD phenotype.
15-19
We examined the possible association between
rs1467568
and
rs7895833
in SIRT1 and BMI, and levels of total cholesterol,
LDL, HDL, triglycerides, fasting glucose, fasting insulin, HbA
1c
,
hsCRP, or IL-6 in CAD patients and control groups, but did not
observe any association.
The Rotterdam study investigated SIRT1 variation (assessed
by three tagging SIRT1 SNPs:
rs7895833
,
rs1467568
and
rs497849
) in relation to BMI and risk of obesity in 4 573
participants, including 413 individuals with prevalent and 378
with incident type 2 diabetes mellitus (T2DM).
20
In homozygous
carriers with prevalent T2DM, the SIRT1 haplotype 1 had
1.9 times (95% CI: 1.1–3.2) increased risk of CVD mortality
compared to non-carriers.
Table 1.
SIRT1 rs1467568
and
rs7895833
genotype and allele
frequencies in CAD patients and controls
SIRT1 rs1467568
CAD
patients
(
n
=
104)
n
, (%)
SA Indian
controls
(
n
=
99)
n
, (%)
Total SA
Indians
(
n
=
203)
n
, (%)
SA black
controls
(
n
=
84)
n
, (%)
Genotypes
AA
40 (38.46)
36 (36.36)
76 (37)
62 (73.81)
AG
42 (40.38)
46 (46.46)
88 (43)
13 (15.48)
GG
22 (21.15)
17 (17.17)
39 (19)
9 (10.71)
Alleles
A
122 (59)
118 (60)
240 (59)
137 (81.5)
G
86 (41)
80 (40)
166 (41)
31 (18.5)
SIRT1 rs7895833 (
n
=
100)
(
n
=
99)
(
n
=
199)
(
n
=
82)
Genotypes
AA
36 (36)
34 (34.34)
70 (35)
47 (57.32)
AG
47 (47)
48 (48.48)
95 (48)
34 (41.46)
GG
17 (17)
17 (17.17)
34 (17)
1 (1.22)
Alleles
A
119 (59.5)
116 (59)
235 (59)
128 (78)
G
81 (40.5)
82 (41)
163 (41)
36 (22)
Table 2. Characteristics of CAD patients according to the
SIRT1 rs1467568
and
SIRT1 rs7895833
genotypes
SIRT1 rs1467568
genotype
p-
value
SIRT1 rs7895833
genotype
p-
value
Wild type (AA) Variant (AG+GG)
Wild type (AA) Variant (AG+GG)
BMI (kg/m
2
)
27.52
±
0.81
28.57
±
0.55
ns
28.02
±
0.80
28.33
±
0.59
ns
Total cholesterol (mmol/l)
5.73
±
0.32
5.17
±
0.20
ns
5.32
±
0.24
5.46
±
0.25
ns
LDL (mmol/l)
3.70
±
0.29
3.27
±
0.21
ns
3.41
±
0.23
3.47
±
0.24
ns
HDL (mmol/l)
0.98
±
0.04
0.89
±
0.03
ns
0.91
±
0.04
0.93
±
0.04
ns
Triglycerides (mmol/l)
2.41
±
0.28
2.37
±
0.18
ns
2.34
±
0.24
2.38
±
0.20
ns
Fasting glucose (mmol/l)
6.48
±
0.50
6.27
±
0.33
ns
6.18
±
0.47
6.32
±
0.34
ns
Fasting insulin (
μ
lU/ml)
16.97
±
2.21
15.54
±
1.12
ns
14.17
±
1.19
16.95
±
1.61
ns
HBA
1c
(%)
6.63
±
0.33
6.61
±
0.24
ns
6.57
±
0.34
6.60
±
0.24
ns
hsCRP (mg/l)
9.83
±
2.58
6.97
±
0.98
ns
8.93
±
2.42
7.78
±
1.31
ns
IL-6 (pg/ml)
2.80
±
0.90
2.45
±
0.59
ns
2.41
±
0.80
2.73
±
0.68
ns
BMI
=
body mass index, LDL
=
low-density lipoprotein, HDL
=
high-density lipoprotein, HBA
1c
=
glycated haemoglobin, hsCRP
=
high-sensitivity C-reactive protein,
IL-6
=
interleukin-6, ns
=
non-significant.
Table 3. Characteristics of Indian controls according to the
SIRT1 rs1467568
and
SIRT1 rs7895833
genotype
SIRT1 rs1467568
genotype
p-
value
SIRT1 rs7895833
genotype
p-
value
Wild type (AA) Variant (AG+GG)
Wild type (AA) Variant (AG+GG)
BMI (kg/m
2
)
25.88
±
0.93
26.65
±
0.69
ns
25.14
±
1.01
26.88
±
0.66
ns
Total cholesterol (mmol/l)
5.32
±
0.16
5.54
±
0.13
ns
5.56
±
0.19
5.41
±
0.12
ns
LDL (mmol/l)
3.47
±
0.13
3.86
±
0.12
ns
3.88
±
0.17
3.63
±
0.11
ns
HDL (mmol/l)
1.04
±
0.07
0.91
±
0.03
ns
0.97
±
0.07
0.95
±
0.03
ns
Triglycerides (mmol/l)
1.79
±
0.22
1.92
±
0.27
ns
1.63
±
0.17
2.00
±
0.27
ns
Fasting glucose (mmol/l)
5.59
±
0.34
5.38
±
0.16
ns
5.27
±
0.20
5.56
±
0.22
ns
Fasting insulin (
μ
lU/ml)
15.91
±
1.96
16.72
±
1.66
ns
13.36
±
1.46
18.03
±
1.75
ns
HBA
1c
(%)
5.78
±
0.21
5.65
±
0.11
ns
5.85
±
0.16
5.63
±
0.13
ns
hsCRP (mg/l)
4.58
±
0.60
7.95
±
1.71
ns
6.52
±
1.41
6.87
±
1.57
ns
IL-6 (pg/ml)
2.16
±
0.79
2.86
±
0.63
ns
2.83
±
0.87
2.48
±
0.60
ns
BMI
=
body mass index, LDL
=
low-density lipoprotein, HDL
=
high-density lipoprotein, HBA
1c
=
glycated haemoglobin, hsCRP
=
high-sensitivity C-reactive protein,
IL-6
=
interleukin-6, ns
=
non-significant.