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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 27, No 4, July/August 2016

216

AFRICA

An intended replication study (Erasmus Rucphen family

study) was carried out involving 2 347 participants. Both

studies observed that the minor alleles of

rs7895833

(G allele)

and

rs1467568

(A allele) were associated with lower BMI and

a 13–18% decreased risk of obesity in two independent Dutch

populations.

17

In another study, the A allele of

rs7895833

was

associated with increased risk of obesity and hypertension in

Japanese men.

15

Recent studies investigated the association between SIRT1

SNPs (

rs7895833

,

rs7069102

,

rs144124002

and

rs2273773

) and

CAD in a Turkish population. While

rs7069102

,

rs2273773

and

rs144124002

were significantly associated with increased risk for

CAD, they found no association between

rs7895833

and CAD.

21,22

Shimoyama

et al.

reported that SIRT1

rs7069102

and

rs2273773

were associated with abnormal cholesterol metabolism

and coronary artery calcification, respectively, in Japanese

haemodialysis (HD) patients. The study also found that the A

allele frequency of SIRT1

rs7895833

and G allele frequency of

rs7069102

were significantly lower in HD patients compared to

controls, suggesting an impact on survival.

19

The allele frequencies of

rs7895833

and

rs1467568

show

ethnic variation, and this is a possible reason for differing disease

patterns among populations. The frequency of the

rs7895833

A allele was relatively low (0.29) in Japanese compared to

Dutch, Turkish and Caucasian subjects who had similar allele

frequencies (0.80, 0.85 and 0.80, respectively).

15,17,23

The A allele

of

rs1467568

(reported as the protective allele) showed marked

difference in frequency between European (0.25) and Japanese

(0.84) subjects.

23

Conclusion

Both SNP variant alleles occurred more frequently in SA Indians

than in SA blacks, but no difference was found between CAD

patients and controls. This study is limited by sample size and

a larger study may be required to fully assess the functional

significance of these polymorphisms.

P Ramkaran thanks the National Research Foundation (NRF) for a scholar-

ship and UKZN (College of Health Sciences) for funding this study.

References

1.

Preyat N, Leo O. Sirtuin deacylases: a molecular link between metabo-

lism and immunity.

J Leukocyte Biol

2013;

93

(5): 669–680.

2.

Cui Y, Wang H, Chen H, Pang S, Liu D, Yan B. Genetic analysis of the

SIRT1 gene promoter in myocardial infarction.

Biochem Biophys Res

Commun

2012;

426

(2): 232–236.

3.

Morris BJ. Seven sirtuins for seven deadly diseases ofaging.

Free Radical

Biol Med

2013;

56

: 133–171.

4.

Stein S, Matter CM. Protective roles of SIRT1 in atherosclerosis.

Cell

Cycle

2011;

10

(4): 640–647.

5.

Li X, Zhang S, Blander S, Tse JG, Krieger M, Guerente L. SIRT1

deacetylates and positively regulates the nuclear receptor LXR.

Molec

Cell

2007;

28

(1): 91–106.

6.

Finkel T. Deng C-X, Mostoslavsky R. Recent progress in the biology

and physiology of sirtuins.

Nature

2009;

460

(7255): 587–591.

7.

Haigis MC, Sinclair DA. Mammalian sirtuins: biological insights and

disease relevance.

A Rev Pathol Mechan Dis

2010;

5

(1): 253–295.

8.

Horio Y, Hayashi T, Kuno A, Kunomoto R. Cellular and molecular

effects of sirtuins in health and disease.

Clin Sci

2011;

121

(5): 191–203.

9.

Houtkooper RH, Pirinen E, Auwerx J. Sirtuins as regulators of metabo-

lism and healthspan.

Nat Rev Mol Cell Biol

2012;

13

(4): 225–238.

10. Norman RBD, Pieterse SMD, Groenwald P. Revised burden of disease

estimates for the comparative risk factor assessment, South Africa 2000.

Cape Town: Medical Research Council, 2006.

11. Sambrook J, Russell DW.

Rapid Isolation of Mammalian DNA in

Molecular Cloning: A Laboratory Manual

. 3rd edn. New York: Cold

Spring Harbor Laboratory Press, 2001.

12. Phulukdaree A, Khan S, Moodley D, Chuturgoon AA. GST polymor-

phisms and early-onset coronary artery disease in young South African

Indians.

S Afr Med J

2012;

102

(7): 627–630.

13. Sharma MGM. Premature coronary artery disease in Indians and its

associated risk factors.

Vasc Health Risk Mgmt

2005;

1

(3): 217–225.

14. Ma L, Li Y. SIRT1: Role in cardiovascular biology.

Clin Chim Acta

2015;

440

: 8–15.

15. Shimoyama Y, Suzuki K, Hamazima N, Niwa T. Sirtuin 1 gene poly-

morphisms are associated with body fat and blood pressure in Japanese

.

Translat Res

2011;

157

(6): 339–347.

16. Peeters A, Beeckers S, Verrijken A, Mertens I, Roevens P, Peeters PJ,

et

al

. Association of SIRT1 gene variation with visceral obesity

. Human

Genet

2008;

124

(4): 431–436.

17. Zillikens MC, van Meurs JB, Rivadeneira F, Amin N, Hofman A,

Oostra BA,

et al

. SIRT1 Genetic variation is related to BMI and risk of

obesity.

Diabetes

2009;

58

(12): 2828–2834.

18. Botden IPG, Zillikens MC, de Rooij SR, Langendonk JG, Danser AHJ,

Sibrands EJG,

et al

. Variants in the SIRT1 gene may affect diabetes risk

in interaction with prenatal exposure to famine

.

Diabetes Care

2012;

35

(2): 424–426.

19. Shimoyama Y, Mitsuda Y, Tsuruta Y, Suzuki K, Hamzima N, Niwa

Table 4. Characteristics of black 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

)

25.53

±

0.54

27.13

±

1.20

ns

25.58

±

0.63

26.57

±

0.87

ns

Total cholesterol (mmol/l)

4.12

±

0.12

4.47

±

0.23

ns

4.30

±

0.13

4.14

±

0.18

ns

LDL (mmol/l)

2.62

±

0.10

3.02

±

0.22

ns

2.78

±

0.12

2.71

±

0.16

ns

HDL (mmol/l)

1.05

±

0.045

1.03

±

0.088

ns

1.08

±

0.05

0.99

±

0.06

ns

Triglycerides (mmol/l)

0.99

±

0.072

0.93

±

0.15

ns

0.98

±

0.08

0.96

±

0.11

ns

Fasting glucose (mmol/l)

4.80

±

0.084

4.90

±

0.11

ns

4.87

±

0.11

4.77

±

0.08

ns

Fasting insulin (

μ

lU/ml)

7.69

±

0.67

12.11

±

3.74

ns

9.21

±

1.73

8.59

±

1.10

ns

HBA

1c

(%)

5.83

±

0.062

5.79

±

0.082

ns

5.87

±

0.07

5.76

±

0.077

ns

hsCRP (mg/l)

6.64

±

1.86

5.82

±

1.23

ns

7.81

±

2.42

4.83

±

0.84

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.