Abstract:
BACKGROUND : Sirtuin 1 (SIRT1), a class III histone deacetylase,
has been identified as a candidate molecule affecting
the epigenetic mechanisms of cardiovascular disease (CVD).
Previous studies have shown that some SIRT1 single-nucleotide
polymorphisms (SNPs) are associated with body mass
index, diabetes, blood pressure, cholesterol metabolism and
coronary artery calcification. We investigated two A>G SIRT1
SNPs, rs1467568 and rs7895833, in young South African (SA)
Indians with coronary artery disease (CAD) and compared
them to Indian and black controls.
METHODS : For rs1467568, a total of 287 subjects were recruited
into this study (104 CAD patients, 99 age-, gender- and
race-matched controls, and 84 age- and gender-matched black
controls). For rs7895833, a total of 281 subjects were recruited
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.
RESULTS : The variant allele for both SNPs was found at a higher
frequency in the total Indian group compared to the total
black population (rs1467568: 41 vs 18.5%, respectively, p <
0.0001, OR = 3.190, 95% CI: 2.058–40943; and rs7895833: 41
vs 22%, respectively, p < 0.0001, OR = 2.466, 95% CI: 1.620–
3.755). Indian controls presented with a higher frequency
for both SNPs compared to black controls (rs1467568: 40 vs
18.5%, respectively, p < 0.0001, OR = 2.996, 95% CI: 1.850–
4.853; and rs7895833: 41 vs 22%, respectively, p < 0.0001, OR = 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.
CONCLUSION : Both SNP variant alleles occurred more frequently
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.
