A study on the association of TNF-α(-308), IL-6(-174), IL-10(-1082) and IL-1Ra(VNTR) gene polymorphisms with rheumatic heart disease in Pakistani patients.
Predisposition to RHD is influenced by genetic factors including cytokine gene polymorphisms, with possible susceptibility to severe disease with multivalvular affection among cases with composite polymorphism (TNF-alpha(-308 )A/A and IL-10(-1082) A/A) and (TNF-alpha(-308 )A/A and IL-10(-1082) G/G).
Predisposition to RHD is influenced by genetic factors including cytokine gene polymorphisms, with possible susceptibility to severe disease with multivalvular affection among cases with composite polymorphism (TNF-alpha(-308 )A/A and IL-10(-1082) A/A) and (TNF-alpha(-308 )A/A and IL-10(-1082) G/G).
Compared with normal subjects, increased IL-10 level and decreased GH were found in RA group whereas unchanged IL-10 and decreased GH were found in RHD group.
Patients with RHD have a higher frequency of DR11-05-DQ7 haplotype and a lower frequency of DR4-03-DQ4 haplotype, which indicates that certain HLA DRB1-DQA1-DQB1 haplotypes in determining the risk/protection of RHD in Taiwan Chinese.
DQ alleles in linkage disequilibrium with DR alleles appear to influence risk/protection effect: whereas the DRB1*13-DQA1*0501-3-DQB1*0301 haplotype showed a trend toward risk, the DRB1*13-DQA1*0103-DQB1*0603 haplotype was absent in the RHD sample.
Multifactor dimensionality reduction and classification and regression tree approaches were combined with logistic regression to discover high-order gene-gene interactions in studiedgenes involved in RHD susceptibility.In univariate logistic regression analysis, we found significant association of variant-containing genotypes (CT&TT) of TGF-β1869T/C [rs1982073]; [p=0.0.004 & 0.001, OR (95% CI)=1.65 (1.2-2.3) & 2.25 (1.4-3.6) respectively], variant genotype (CC) of IL-1β -511C/T [rs2853550]; [p=0.001, OR (95% CI)=2.33 (1.4-3.8)] and IL-1 VNTR [rs2234663]; [p=0.03, OR (95% CI)=5.25 (1.2-23.4)] SNPs with RHD risk.
In conclusion, an ongoing inflammatory process, the expression of TGF-beta 1, and proliferation of myofibroblasts within the valves have a potential role in the valvular fibrosis, calcification, and changes in the extracellular matrix that lead to the scarring sequelae of rheumatic heart disease.
A significant difference was seen in the distribution of allelic frequency between patients with RHD and control patients for TGF-beta1T869C polymorphism (P =.04).
In the present study, by next generation sequencing of miRNAs, it was revealed that interleukin 1β and interleukin 1 receptor 1 was involved in rheumatic heart diseases.
In addition, pro-inflammatory cytokine profile revealed high levels of interleukin-12 (IL-12)/IL-23p40, IL-17A in RF, whereas IL-6 concentration was higher in RHD compared to healthy controls.