Gene polymorphisms of TNF-α and IL-10 related to rheumatic heart disease

Abstract

Background: Rheumatic fever (RF) is inherited as a single recessive gene. Several genes are Likely to predispose an individual to develop rheumatic fever and rheumatic heart disease (RHD). Polymorphisms of TNF-α gene were associated with susceptibility to develop RF.T cells from all rheumatic fever patients produce significant amounts of TNF-α in response to steptococcal peptides with the highest production attained by the chronic rheumatic heart disease patients,and IL-10 expression was characterized in heart tissue of RHD patients by immuno-histochemistry. Objectives: To test the relation of RHD and gene polymorphisms of pro-inflammatory cytokines TNF-α gene at position -308 and anti–inflammatory IL-10 gene at position -1082. Subjects and Methods: This study included 20 children with chronic rheumatic heart disease (group A) and 10 healthy children as a control group (Group B). Patients group was classified into patients with single and multiple valvular lesions, both of them were classified according to the severity by Echocardiography into: Group I: mild valvular lesion (n=7) Group II: Moderate lesion (n=4) Group III: severe lesion (n=9) Real time PCR was done for both TNF-α at-308 and IL-10 at position – 1082.
Results: All cases showed significant higher frequency of TNF-α homozygous genotype G/G compared to control group (p <0.05,OR,11). Cases with severe valvular lesions showed increased frequency of homozygous genotype G/G and increased frequency of IL-10 genotype G/A in cases compared to control group (p ≤0.05,OR 13). There was no statistically significant difference in frequency of IL-10 genotypes among cases and control groups regarding to severity of valvular lesions. Composite genotypes (TNF-α G/G,IL-10 G/A) were higher in cases compared to control group (P ≤ 0.01), while composite genotypes (TNF-α G/A,IL -10 G/G) were higher in control group compared to cases groups. Conclusions: Susceptibility to RHD is associated with cytokine gene polymorphisms of TNF-α homozygous genotype G/G at-308 and IL-10 G/A at 1082. Composite genotypes (TNF-α G/G,IL-10 G/A) had high risk for RHD, while composite genotypes (TNF-α G/A,IL-10 G/G) may be protective genotypes.

Key Words: Rheumatic fever, rheumatic, heart disease, TNF-α, IL-10 gene polymorphisms.