CARDIOVASCULAR JOURNAL OF AFRICA • Volume 27, No 4, July/August 2016
in South African
Indians with early-onset coronary artery disease
Prithiksha Ramkaran, Alisa Phulukdaree, Sajidah Khan, Devapregasan Moodley, Anil A Chuturgoon
Sirtuin 1 (SIRT1), a class III histone deacetyl-
ase, has been identified as a candidate molecule affecting
the epigenetic mechanisms of cardiovascular disease (CVD).
Previous studies have shown that some SIRT1 single-nucle-
otide polymorphisms (SNPs) are associated with body mass
index, diabetes, blood pressure, cholesterol metabolism and
coronary artery calcification. We investigated two A
, in young South African (SA)
Indians with coronary artery disease (CAD) and compared
them to Indian and black controls.
, a total of 287 subjects were recruit-
ed into this study (104 CAD patients, 99 age-, gender- and
race-matched controls, and 84 age- and gender-matched black
, a total of 281 subjects were recruit-
ed into this study (100 CAD patients, 99 age-, gender- and
race-matched controls, and 82 age- and gender-matched black
controls). All patients were male, of Indian ethnicity, stable CAD
confirmed on angiography, mean age 37.5 years; range 24–45. All
subjects were genotyped using TaqMan SNP genotyping assays.
The variant allele for both SNPs was found at a higher
frequency in the total Indian group compared to the total
black population (
: 41 vs 18.5%, respectively,
3.190, 95% CI: 2.058–40943; and
vs 22%, respectively,
2.466, 95% CI: 1.620–
3.755). Indian controls presented with a higher frequency
for both SNPs compared to black controls (
: 40 vs
2.996, 95% CI: 1.850–
: 41 vs 22%, respectively,
2.513, 95% CI: 1.578–4.004). No difference was seen in the
distribution of both SNPs between CAD patients and either
control group. We did not observe any association between the
SNPs and clinical parameters in CAD patients and controls.
Both SNP variant alleles occurred more frequent-
ly in SA Indians than in SA blacks. A larger study group and
further analysis is required to assess whether these SIRT1
SNPs may serve as risk factors that contribute to Indians
developing early-onset CAD.
polymorphism, premature coronary artery disease, South
Submitted 22/4/15, accepted 14/11/15
Cardiovasc J Afr
Sirtuins are a class of NAD
-dependent proteins involved in a
wide range of biological processes such as aging, transcription,
apoptosis and inflammation.
Sirtuin 1 (SIRT1) is located in
the nucleus and cytoplasm, and plays an important role in
epigenetic regulation by deacetylating a range of transcription
factors to control downstream gene expression.
of SIRT1 include Forkhead box O (FOXO)1, (FOXO)3,
peroxisome proliferator-activated receptor gamma coactivator
), tumour suppressor p53, nuclear factor-
kappa B (NF-
B), Notch, hypoxia-inducible factor (HIF) 1
liver X receptor (LXR), farnesoid X receptor (FXR) and sterol
regulatory element-binding protein (SREBP)1c.
Recent studies have demonstrated a protective role of SIRT1
in atherosclerosis, the underlying process of coronary artery
SIRT1 performs an anti-inflammatory function
by downregulating the expression of several pro-inflammatory
cytokines by interfering with the NF-
B signalling pathway.
By deacetylating NF-
B, SIRT1 suppresses the expression of
lectin-like oxidised low-density lipoprotein receptor-1 (Lox-
1), a scavenger receptor for oxidised low-density lipoproteins
(oxLDL), therefore preventing foam cell formation.
controls the activity of LXR, an important regulator of lipid
homeostasis and inflammation.
Activation of LXR results in
expression of ATP-binding cassette (ABC) transporter ABCA1,
which regulates the removal of cholesterol into high-density
lipoproteins (HDL), a process known as reverse cholesterol
transport (RCT). Dysfunctional RCT could lead to accumulation
of cholesterol, thus stimulating foam cell production and the
progression of atherosclerosis.
Given the important role of
SIRT1 in cardiovascular disease, research on genetic variation in
the SIRT1 gene has become of interest.
Genetic variations such as single-nucleotide polymorphisms
(SNPs) in the SIRT1 gene have been associated with
inflammation, body mass index, type 2 diabetes, blood pressure
and dyslipidaemia, all of which are well-established risk factors
Coronary artery disease remains a leading cause of
mortality worldwide, with an unusually high prevalence of early-
onset disease among the Indian population. South African (SA)
Indians have a much higher prevalence of CAD compared to SA
There are currently no studies on SIRT1 SNPs in SA
Indians with CAD. We therefore investigated the SIRT1 A
in young SA Indians with CAD
and compared them to Indian and black controls.
Discipline of Medical Biochemistry and Chemical Pathology,
University of KwaZulu-Natal, Durban, South Africa
Prithiksha Ramkaran, BMedSc Hons
Devapregasan Moodley, PhD
Anil A Chuturgoon, PhD,firstname.lastname@example.org
Department of Physiology, School of Medicine, Faculty of
Health Sciences, University of Pretoria, South Africa
Alisa Phulukdaree, PhD
Department of Cardiology, Nelson R Mandela School of
Medicine, University of KwaZulu-Natal, Durban, South Africa
Sajidah Khan, MB ChB, FCP (SA), PhD