Cytokine gene polymorphisms in the susceptibility to acute coronary syndrome

Abstract

Aim: Acute coronary syndrome (ACS) is an inflammatory disease. Cytokines are the central regulators of inflammation and may be a cause or marker of atherosclerosis. Accumulating evidence suggests that polymorphisms at promoter regions of various cytokine genes are known to be associated with their expression levels. In the present study we investigated whether variants at -1082G→A (rs1800896) and -592C→A (rs1800872) of interleukin-10 (IL-10), -1188A→C (rs3212227) of IL-12 p40, -308G→A of tumor necrosis factor-α (TNF-α) (rs1800629), -174G→C of IL-6 (rs1800795) and +874A→T of interferon-γ (IFN-γ) genes (rs2430561) are associated with ACS.

Materials and methods: DNA samples were collected from 1083 subjects and IL-10-1082G→A, -592A→C, TNF-α-308G→A, IL-12 p40-1188 A→C, and IFN-γ+874A→T polymorphisms were identified by amplified refractory mutation system polymerase chain reaction and IL-6-174 G/C, restriction fragment length polymorphism based on standard methods.

Results: Six hundred and fifty one ACS patients along with 432 age and sex matched controls were analyzed for various gene polymorphisms. The "low-producer" IL-10-1082 AA (χ(2)=9.45; p=0.0021; odds ratio [OR]=1.472; 95% confidence interval [CI]=1.15-1.884), "high producer" IL-10-592 CC (χ(2)=39.42; p=0.001, OR=2.26; 95% CI=1.748-2.292), "low producer"IFN-γ+874AA (χ(2)=28; p<0.00154; OR=2.36 & 95% CI=1.713-3.251), and "high producer" TNF-α -308AA (χ(2)=3.213, p=0.073; OR=1.515) genotypes may be responsible for the regulation of immune response leading to inflammation in ACS patients. However, -1188 of the IL-12 gene was not associated with the disease.

Conclusion: The polymorphisms at -308G→A of TNF-α, -174G→C of IL-6, +874A→T of IFN-γ and -1082G→A, and -592C→A of IL-10 genes evaluated in the present study are important risk factors for the development of ACS in the South Indian population from Andhra Pradesh. The better understanding of these variants conferring susceptibility to ACS may aid in early diagnosis and development of new methods to create personalized medicine.