Promoter variants of TNF-α rs1800629 and IL-10 rs1800871 are independently associated with the susceptibility of coronary artery disease in north Indian.

ABSTRACT

BACKGROUND: Tumor necrosis factor-alpha (TNF-α) are considered as a pro inflammatory and interleukin-10 (IL-10) anti inflammatory have been shown to predict the risk of incident of coronary artery disease (CAD). The polymorphism at promoter of TNF-α and IL-10 has been shown to increase transcriptional activity of the gene and play a important role in patho physiology of CAD. Aim of present study is to examine the impact of the TNF-α and IL-10 variant allele on various markers of the CAD and to study its relation with circulating TNF-α and IL-10 levels. METHODS: The -308 G/A & -238 G/A of TNF-α and -1082 G/A & -819 C/T of IL-10 gene polymorphism has been studied in 301 diagnosed CAD subjects (Age 51.50 ±â€¯9.28; BMI 25.30 ±â€¯3.58) and 305 healthy controls (Age 51.57 ±â€¯9.50; BMI 24.06 ±â€¯7.26). These polymorphism of TNF-α and IL-10 were detected by real time PCR by using Taqman SNP genotyping assay. Furthermore serum TNF-alpha and IL-10 levels were also measured by ELISA. RESULTS: Allelic and genotypic frequencies did not deviate from Hardy-Weinberg equilibrium in the controls (p > 0.05). On allele contrast, significant association with susceptibility to CAD was detected with polymorphisms in TNF-α -308 G/A, that variant genotype GA + AA (dominant model) (p = 0.030 OR = 1.61 95% CI = 1.06-2.44) and variant allele (A) (p = 0.006 OR = 1.71 95% CI = 1.17-2.51) of TNF-α 308 G/A gene was significant highly observed in the cases as compared to control group. Furthermore, variant genotype CT + TT (dominant model) (p = 0.004 OR = 1.62 95% CI = 1.17-2.24) and variant allele (T) (p < 0.001 OR = 1.49 95% CI = 1.17-1.89) of IL-10 -819 C/T gene was significant highly observed in the cases as compared to control group. CONCLUSION: Our results suggest that the TNF-α G-308A polymorphism independently associated with DBP, cholesterol, triglyceride, LDL, TNF-α and IL-10 levels which may be leads to the development of coronary artery disease of North Indians.