Inflammatory bowel diseases (IBD) are complex multifactorial disorders that include Crohn’s disease (CD) and ulcerative colitis (UC). Considering that IBD is a genetic and multifactorial disease, we screened for the ...Inflammatory bowel diseases (IBD) are complex multifactorial disorders that include Crohn’s disease (CD) and ulcerative colitis (UC). Considering that IBD is a genetic and multifactorial disease, we screened for the distribution dynamism of IBD pathogenic genetic variants (single nucleotide polymorphisms;SNPs) and risk factors in four (4) IBD pediatric patients, by integrating both clinical exome sequencing and computational statistical approaches, aiming to categorize IBD patients in CD and UC phenotype. To this end, we first aligned genomic read sequences of these IBD patients to hg19 human genome by using bowtie 2 package. Next, we performed genetic variant calling analysis in terms of single nucleotide polymorphism (SNP) for genes covered by at least 20 read genomic sequences. Finally, we checked for biological and genomic functions of genes exhibiting statistically significant genetic variant (SNPs) by introducing Fitcon genomic parameter. Findings showed Fitcon parameter as normalizing IBD patient’s population variability, as well as inducing a relative good clustering between IBD patients in terms of CD and UC phenotypes. Genomic analysis revealed a random distribution of risk factors and as well pathogenic SNPs genetic variants in the four IBD patient’s genome, claiming to be involved in: i) Metabolic disorders, ii) Autoimmune deficiencies;iii) Crohn’s disease pathways. Integration of genomic and computational statistical analysis supported a relative genetic variability regarding IBD patient population by processing IBD pathogenic SNP genetic variants as opposite to IBD risk factor variants. Interestingly, findings clearly allowed categorizing IBD patients in CD and UC phenotypes by applying Fitcon parameter in selecting IBD pathogenic genetic variants. Considering as a whole, the study suggested the efficiency of integrating clinical exome sequencing and computational statistical tools as a right approach in discriminating IBD phenotypes as well as improving inflammatory bowel disease (IBD) molecular diagnostic process.展开更多
Idiopathic membranous nephropathy (IMN) is a Th2 nephritogenic immune disorder. It is caused by the accumulation of immune complexes, mainly IgG4, at the basal glomerular membrane that leads to the damage of the glome...Idiopathic membranous nephropathy (IMN) is a Th2 nephritogenic immune disorder. It is caused by the accumulation of immune complexes, mainly IgG4, at the basal glomerular membrane that leads to the damage of the glomerular barrier and subsequent injury of podocytes. Our aim was to evaluate the relationship between cytokine polymorphisms and IMN. We investigated the cytokine polymorphisms in forty-five patients and one hundred twenty-four healthy individuals, using polymerase chain reaction-sequence specific primers (PCR-SSP). We showed a significant increase in allelic frequencies of the alleles -590T and -33T of IL-4 gene and -308A of TNF-α gene, in IMN patients. In addition, we observed an increased frequency of allele -1082G in IL-10 gene in a subgroup of patients with CD4/CD8 ratio major than 2, when compared either to control subjects or the subgroup of patients with CD4/CD8 ratio minor than 2. Moreover, analyzing the Th1/Th2 cytokines in serum and urine, we found increased levels of IL-4 in serum and IL-5 in urine of patients. We deduce that the alleles -590T and -33T of IL-4 and -308A of TNF-α may be associated with IMN. In addition, in patients with increased T helper lymphocytes, IL-10 -1082G polymorphism can also play a role in the pathogenesis of the disease. These findings remark the role of Th2 immune response and suggest the association between polymorphic variants of IL-4, IL-10 and TNF-α genes with the development of IMN and therefore giving a better insight in pathogenesis of this disease.展开更多
文摘Inflammatory bowel diseases (IBD) are complex multifactorial disorders that include Crohn’s disease (CD) and ulcerative colitis (UC). Considering that IBD is a genetic and multifactorial disease, we screened for the distribution dynamism of IBD pathogenic genetic variants (single nucleotide polymorphisms;SNPs) and risk factors in four (4) IBD pediatric patients, by integrating both clinical exome sequencing and computational statistical approaches, aiming to categorize IBD patients in CD and UC phenotype. To this end, we first aligned genomic read sequences of these IBD patients to hg19 human genome by using bowtie 2 package. Next, we performed genetic variant calling analysis in terms of single nucleotide polymorphism (SNP) for genes covered by at least 20 read genomic sequences. Finally, we checked for biological and genomic functions of genes exhibiting statistically significant genetic variant (SNPs) by introducing Fitcon genomic parameter. Findings showed Fitcon parameter as normalizing IBD patient’s population variability, as well as inducing a relative good clustering between IBD patients in terms of CD and UC phenotypes. Genomic analysis revealed a random distribution of risk factors and as well pathogenic SNPs genetic variants in the four IBD patient’s genome, claiming to be involved in: i) Metabolic disorders, ii) Autoimmune deficiencies;iii) Crohn’s disease pathways. Integration of genomic and computational statistical analysis supported a relative genetic variability regarding IBD patient population by processing IBD pathogenic SNP genetic variants as opposite to IBD risk factor variants. Interestingly, findings clearly allowed categorizing IBD patients in CD and UC phenotypes by applying Fitcon parameter in selecting IBD pathogenic genetic variants. Considering as a whole, the study suggested the efficiency of integrating clinical exome sequencing and computational statistical tools as a right approach in discriminating IBD phenotypes as well as improving inflammatory bowel disease (IBD) molecular diagnostic process.
文摘Idiopathic membranous nephropathy (IMN) is a Th2 nephritogenic immune disorder. It is caused by the accumulation of immune complexes, mainly IgG4, at the basal glomerular membrane that leads to the damage of the glomerular barrier and subsequent injury of podocytes. Our aim was to evaluate the relationship between cytokine polymorphisms and IMN. We investigated the cytokine polymorphisms in forty-five patients and one hundred twenty-four healthy individuals, using polymerase chain reaction-sequence specific primers (PCR-SSP). We showed a significant increase in allelic frequencies of the alleles -590T and -33T of IL-4 gene and -308A of TNF-α gene, in IMN patients. In addition, we observed an increased frequency of allele -1082G in IL-10 gene in a subgroup of patients with CD4/CD8 ratio major than 2, when compared either to control subjects or the subgroup of patients with CD4/CD8 ratio minor than 2. Moreover, analyzing the Th1/Th2 cytokines in serum and urine, we found increased levels of IL-4 in serum and IL-5 in urine of patients. We deduce that the alleles -590T and -33T of IL-4 and -308A of TNF-α may be associated with IMN. In addition, in patients with increased T helper lymphocytes, IL-10 -1082G polymorphism can also play a role in the pathogenesis of the disease. These findings remark the role of Th2 immune response and suggest the association between polymorphic variants of IL-4, IL-10 and TNF-α genes with the development of IMN and therefore giving a better insight in pathogenesis of this disease.
