title: Sirtuin 1 rs1467568 and rs7895833 in South African Indians with early-onset coronary artery disease.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Discipline of Medical Biochemistry and Chemical Pathology, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: Prithiksha
authors.initials: P
authors.lastname: Ramkaran
authors.affiliation: Department of Physiology, School of Medicine, Faculty of Health Sciences, University of Pretoria, South Africa.
authors.forename: Alisa
authors.initials: A
authors.lastname: Phulukdaree
authors.affiliation: Department of Cardiology, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: Sajidah
authors.initials: S
authors.lastname: Khan
authors.affiliation: Discipline of Medical Biochemistry and Chemical Pathology, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: Devapregasan
authors.initials: D
authors.lastname: Moodley
authors.affiliation: Discipline of Medical Biochemistry and Chemical Pathology, University of KwaZulu-Natal, Durban, South Africa. Email: chutur@ukzn.ac.za.
authors.forename: Anil A
authors.initials: AA
authors.lastname: Chuturgoon
mesh_terms: D000328:Adult; D017668:Age of Onset; D044383:Black People / Q000235:genetics; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D003324:Coronary Artery Disease / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007194:India / Q000208:ethnology; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D056564:Sirtuin 1 / Q000235:genetics*; D013019:South Africa / Q000453:epidemiology; D055815:Young Adult
chemical_list: C447939:SIRT1 protein, human; D056564:Sirtuin 1