Association Of NF-κB And PXR Gene Polymorphisms And Rheumatic Heart Disease Susceptibility In Chinese Han Population

Aims: Rheumatic heart disease, an autoimmune diseases,a kind of heart calves and myocardial damage caused by beta-hemolytic streptococcus long-term repeated infections. NF-κB is an important transcription factors that regulate the immune response,playing a crucial role in the development and progression of various inflammatory and immune diseases. PXR, attached to a nuclear receptor superfamily,play a protective role on inflammatory and autoimmune disease by inhibitng the expression of target genes of the NF-κB signaling pathway such as IL-10,TNF-a,etc.The aims of our present study were to fiding the relationship between the single nucleotide polymorphisms of NF-κ2B, PXR and rheumatic heart disease.Methods:We performed a case-control study including356patients with rheumatic heart disease and214healthy volunteers. Genomic DNA was exacted from venous blood using DNA extraction kit and the genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and verified by PCR product sequencing. Chi-square test was used to the differences of allelic and genotypic frequencies. At the same time, haplotype analysis and stratified analysis were applied to compare the difference between the cases and controls.Results:All Alleles and genotypes were in line with Hardy-Weinberg equilibrium. Distribution frequencies of NF-κB allele in case and control groups were58.7%,41.3%and53.3%,46.7%, and the difference was not statistically significant (P=0.07). The genotype frequencies of the case and control were35.7%,46.0%,18.3%and27.1%,52.3%,20.6%respectively for II, ID,DD, the distribution ways no significant difference (P=0.11). But under a dominant model, RHD risk of ID/DD genotype was reduced with odds ratio of0.67compared with the Ⅱ genotype(95%CI0.46-0.97, P=0.03).After stratified analyzing of PXR gene, the ID genotype of NF-κB presented a lower frequency in RHD patients than in controls (OR=0.36,95%0.18-0.73, P=0.005). Likewise, the difference was found in Homozygote DD (OR=0.38,95%0.16-0.90, P=0.028). Moreover, linkage disequilibrium of PXR rs3814055, rs6785049two points is weak (D,=0.188, r2=0.008). The frequencies of rs3814055allele C and T were found to be76.5%,23.5%in RHD,75.9%,24.1%in health control, respectively. There was no statistically significant difference between the case and control groups (P=0.81).The distribution of three genotypes was no significant difference (P=0.27) according to the frequency59.0%for CC,35.1%for CT,5.9%for TT and55.6%,40.7%,3.7%, respectively. What is more, no significant difference was discovered in the allelic and genotypic distribution of the PXR rs6785049.Allele frequencies were56.9%for PXR Q43.1%for PXR A in RHD and61.0%for PXR G,39.0%for PXR A in control. And the three genotypes of RHD:32.3%for GG,49.2%for GA,18.5%for AA while the three genotypes of control:37.9%for GG,46.3%for GA,15.9%for AA, respectively.Conclusions:NF-κB gene-94ins/del ATTG mutation was probably associated with rheumatic heart disease in Chinese Han population. And by PXR stratification analysis the distribution of NF-κB gene-94ins/del ATTG variations in RHD subjects and healthy controls were significant differences. The study displayed no association of PXR gene rs3814055and rs6785049with predisposition to rheumatic heart disease.