Genetic Variation in NFKB1 and NFKBIA and Susceptibility to Coronary Artery Disease in a Chinese Uygur Population

Objectives

Coronary artery disease (CAD) is the most common chronic inflammatory disease worldwide. NF-κB, a central regulator of inflammation, is involved in various inflammatory diseases. The aim of this study was to investigate the association between NFKB1 and NFKBIA polymorphisms and the susceptibility to CAD and their impact on plasma levels of IL-6 in a Chinese Uygur population.

Methods

We genotyped NFKB1-94ins/del ATTG (rs28362491) and NFKBIA3’ UTR A/G (rs696) using TaqMan SNP genotyping assays in 960 Uygur CAD cases and Uygur 1060 CAD-negtive controls. IL-6 plasma levels were measured in 360 stable angina pectoris (SAP) cases and 360 controls using ELISA method.

Results

There was no significant difference in the distribution of the genotypes and alleles of rs696 polymorphism in CAD cases and controls. Significant difference in the frequency of genotypes (P = 0.001) and alleles (P = 0.001) of rs28362491 polymorphism was observed in CAD cases compared to controls. In multivariate logistic regression analysis, SNP rs28362491 was consistently associated with CAD risk in a recessive model after adjustment for cardiovascular risk factors (OR = 1.581, 95% CI 1.222 to 2.046, P<0.001). SAP cases had significantly higher plasma levels of IL-6 compared to controls (P<0.001). General linear model analysis showed rs28362491 was independently associated with increased IL-6 levels by analyses of a recessive model (P<0.001) after adjustment for covariates.

Conclusions

Our study indicates that NFKB1-94 ins/del ATTG polymorphism may play a role in CAD susceptibility in Chinese Uygur population and is functionally associated with IL-6 expression, suggesting a mechanistic link between NFKB1-94 ins/del ATTG polymorphism and CAD susceptibility.