Association of Sirtuin Gene Polymorphisms with Susceptibility to Coronary Artery Disease in a North Chinese Population

Abstract

Aims. Coronary artery disease (CAD) represents the leading cause of death worldwide. Accumulating evidence also suggests that sirtuins (SIRTS) have been associated with CAD. The present study was aimed at investigating the association between 12 gene polymorphisms for SIRTs and the development of CAD in a Chinese population. Materials and Methods. 12 SNPs (rs12778366 ( $\text{T}>\text{C}$ ), rs3758391 ( $\text{T}>\text{C}$ ), rs3740051 ( $\text{A}>\text{G}$ ), rs4746720 ( $\text{C}>\text{T}$ ), rs7895833 ( $\text{G}>\text{A}$ ), rs932658 ( $\text{A}>\text{C}$ ) for SIRT1, rs2015 ( $\text{G}>\text{T}$ ) for SIRT2, rs28365927 ( $\text{G}>\text{A}$ ), rs11246020 ( $\text{C}>\text{T}$ ) for SIRT3, rs350844 ( $\text{G}>\text{A}$ ), rs350846 ( $\text{G}>\text{C}$ ), and rs107251 ( $\text{C}>\text{T}$ ) for SIRT6) were selected and assessed in a cohort of 509 CAD patients and 552 matched healthy controls for this study. Genomic DNA from whole blood was extracted, and the SNPs were assessed using MassARRAY method. Results. TT genotype for rs3758391 and GG genotype for rs7895833 of SIRT1 were at higher risk of CAD, whereas the CC genotype for rs4746720 of SIRT1 was associated with a significantly decreased risk of CAD. The A allele of the rs28365927 of SIRT3 showed a significant decreased risk association with CAD patient group ( $P=0.014$ ). Significant difference in genotypes rs350844 ( $\text{G}>\text{A}$ ) ( $P=0.004$ ), rs350846 ( $\text{G}>\text{C}$ ) ( $P=0.002$ ), and rs107251 ( $\text{C}>\text{T}$ ) ( $P\le 0.01$ ) for SIRT6 was also found between the CAD patients and the healthy controls. Haplotype CTA significantly increased the risk of CAD ( $P=0.000118$ , $\text{OR}=1.497$ , $95\%\text{CI}=1.218–1.840$ ), while haplotype GCG significantly decreases the risk of CAD ( $P=0.000414$ , $\text{OR}=1.131$ , $95\%\text{CI}=0.791–1.619$ ). Conclusions. The SNP rs28365927 in the SIRT3 gene and SNP rs350844, rs350846, and rs107251 in the SIRT6 gene present significant associations with CAD in a north Chinese population. Haplotype CTA and GCG generated by rs350846/rs107251/rs350844 in the SIRT6 might also increase and decrease the risk of CAD, respectively.