Rheumatoid arthritis(RA) is an autoimmune disease, resulting in a chronic, systemic inflammatory disorder. It may affect many tissues and organs, but it primarily affects the flexible joints. In clinical practice pati...Rheumatoid arthritis(RA) is an autoimmune disease, resulting in a chronic, systemic inflammatory disorder. It may affect many tissues and organs, but it primarily affects the flexible joints. In clinical practice patient care generates many questions about diagnosis, prognosis, and treatment. It is challenging for health care specialists to keep up to date with the medical literature. This review summarizes the pathogenesis, the polymorphisms of interleukin and interleukin genes and the standard available and possible future immunologictargets for RA treatment. The identification of diseaseassociated interleukin and interleukin receptor genes can provide precious insight into the genetic variations prior to disease onset in order to identify the pathways important for RA pathogenesis. The knowledge of the complex genetic background may prove useful for developing novel therapies and making personalized medicine based on the individual's genetics.展开更多
Inflammatory bowel disease(IBD),which includes Crohn’s disease(CD)and ulcerative colitis(UC),represents a group of chronic inflammatory disorders caused by dysregulated immune responses in genetically predisposed ind...Inflammatory bowel disease(IBD),which includes Crohn’s disease(CD)and ulcerative colitis(UC),represents a group of chronic inflammatory disorders caused by dysregulated immune responses in genetically predisposed individuals.Genetic markers are associated with disease phenotype and long-term evolution,but their value in everyday clinical practice is limited at the moment.IBD has a clear immunological background and interleukins play key role in the process.Almost130 original papers were revised including meta-analysis.It is clear these data are very important for understanding the base of the disease,especially in terms of clinical utility and validity,but text often do not available for the doctors use these in the clinical practice nowadays.We conducted a systematic review of the current literature on interleukin and interleukin receptor gene polymorphisms associated with IBD,performing an electronic search of PubMed Database from publications of the last 10 years,and used the following medical subject heading terms and/or text words:IBD,CD,UC,interleukins and polymorphisms.展开更多
AIM: To investigate the frequency of the common NOD2/CARD15 susceptibility variants and two functional polymorphisms of OCTN cation transporter genes in Hungarian pediatric patients with Crohn’s disease (CD). METHODS...AIM: To investigate the frequency of the common NOD2/CARD15 susceptibility variants and two functional polymorphisms of OCTN cation transporter genes in Hungarian pediatric patients with Crohn’s disease (CD). METHODS: A cohort of 19 unrelated pediatric and 55 unrelated adult patients with Crohn’s disease and 49 healthy controls were studied. Genotyping of the three common CD-associated CARD15 variants (Arg702Trp, Gly908Arg and 1007finsC changes) with the SLC22A4 1672C→T, and SLC22A5 -207G→C mutations was performed by direct sequencing of the specifi c regions of these genes.RESULTS: At least one CARD15 mutation was present in 52.6% of the children and in 34.5% of the adults compared to 14.3% in controls. Surprisingly, strongly different mutation profi le was detected in the pediatric versus adult patients. While the G908R and 1007finsC variants were 18.4% and 21.1% in the pediatric group, they were 1.82% and 11.8% in the adults, and were 1.02% and 3.06% in the controls, respectively. The R702W allele was increased approximately two-fold in the adult subjects, while in the pediatric group it was only approximately 64% of the controls (9.09% in the adults, 2.63% in pediatric patients, and 4.08% in the controls). No accumulation of the OCTN variants was observed in any patient group versus the controls.CONCLUSION: The frequency of the NOD2/CARD15 susceptibility variants in the Hungarian pediatric CD population is high and the profile differs from the adult CD patients, whereas the results for SLC22A4 and SLC22A5 mutation screening do not confirm the assumption that the carriage of these genotypes means an obligatory susceptibility to CD.展开更多
Ulcerative colitis(UC) is one of the main types of inflammatory bowel disease, which is caused by dysregulated immune responses in genetically predisposed individuals. Several genetic factors, including interleukin an...Ulcerative colitis(UC) is one of the main types of inflammatory bowel disease, which is caused by dysregulated immune responses in genetically predisposed individuals. Several genetic factors, including interleukin and interleukin receptor gene polymorphisms and other inflammation-related genes play central role in mediating and modulating the inflammation in the human body, thereby these can be the main cause of development of the disease. It is clear these data are very important for understanding the base of the disease, especially in terms of clinical utility and validity, but summarized literature is exiguous for challenge health specialist that can used in the clinical practice nowadays. This review summarizes the current literature on inflammationrelated genetic polymorphisms which are associated with UC. We performed an electronic search of Pubmed Database among publications of the last 10 years, using the following medical subject heading terms: UC, ulcerative colitis, inflammation, genes, polymorphisms, and susceptibility.展开更多
AIM To investigate the association of seven single nucleotide polymorphisms(SNPs) of the IL23 R gene with the clinical picture of ulcerative colitis(UC). METHODS Genomic DNA samples of 131 patients (66 males, 65 femal...AIM To investigate the association of seven single nucleotide polymorphisms(SNPs) of the IL23 R gene with the clinical picture of ulcerative colitis(UC). METHODS Genomic DNA samples of 131 patients (66 males, 65 females, mean age 55.4 ± 15.8 years) with Caucasian origin, diagnosed with UC were investigated. The diagnosis of UC was based on the established clinical, endoscopic, radiological, and histopathological guidelines. DNA was extracted from peripheral blood leukocytes by routine salting out method. Polymerase chain reaction and restriction fragment length polymorphism were used to identify the alleles of seven SNPs of IL23 R gene(rs11209026, rs10889677, rs1004819, rs2201841, rs7517847, rs10489629, rs7530511).RESULTS Four out of seven analyzed SNPs had statistically significant influence on the clinical picture of UC. Two SNPs were associated with greater colonic extension(rs2201841 P = 0.0084; rs10489629 P = 0.0405). For two of the SNPs, there was more frequently need for operations (rs2201841 P = 0.0348, OR = 8.0; rs10889677 P = 0.0347, OR = 8.0). The rs2201841 showed to be a risk factor for the development of iron deficiency (P = 0.0388, OR = 6.1837). For patients with the rs10889677, a therapy with azathioprine was more frequently necessary(P = 0.0116, OR = 6.1707). Patients with rs10489629 SNP had a lower risk for weight loss(P = 0.0169, OR = 0.3394). Carriers of the heterozygous variant had a higher risk for an extended disease (P = 0.0284). The rs7517847 showed a protective character leading to mild bowel movements. Three SNPs demonstrated no statistically significant influence on any examined clinical features of UC.CONCLUSION We demonstrated susceptible or protective character of the investigated IL23 R SNPs on the phenotype of UC, confirming the genetic association.展开更多
AIM:To investigate the interaction of interleukin-23 receptor(IL23R)(rs1004819 and rs2201841),autophagy-related 16-like 1(ATG16L1)(rs2241880), caspase recruitment domain-containing protein 15 (CARD15)genes,and IBD5 lo...AIM:To investigate the interaction of interleukin-23 receptor(IL23R)(rs1004819 and rs2201841),autophagy-related 16-like 1(ATG16L1)(rs2241880), caspase recruitment domain-containing protein 15 (CARD15)genes,and IBD5 locus in Crohn's disease(CD) patients. METHODS:A total of 315 unrelated subjects with CD and 314 healthy controls were genotyped.Interactions and specific genotype combinations of a total of eight variants were tested.The variants of IBD5locus(IGR2198a_1 rs11739135 and IGR2096a_1 rs12521868),CARD15(R702W rs2066845 and L1007fs rs2066847),ATG16L1(rs2241880)and IL23R (rs1004819,rs2201841)genes were genotyped by PCR-RFLP,the G908R(rs2066844)in CARD15 was determined by direct sequencing. RESULTS:The association of ATG16L1 T300A with CD was confirmed[P=0.004,odds ratio(OR)=1.69, 95%CI:1.19-2.41],and both IL23R variants were found to represent significant risk for the disease(P= 0.008,OR=2.05,95%CI:1.20-3.50 for rs1004819 AA;P<0.001,OR=2.97,95%CI:1.65-5.33 for rs2201841 CC).Logistic regression analysis of pairwise interaction of the inflammatory bowel disease (IBD)loci indicated that IL23R,ATG16L1,CARD15 and IBD5(IGR2198a_1)contribute independently to disease risk.We also analysed the specific combina- tions by pair of individual ATG16L1,IL23R rs1004819, rs2201841,IGR2198a_1,IGR2096a_1 and CARD15 genotypes for disease risk influence.In almost all cases,the combined risk of susceptibility pairs was higher in patients carrying two different risk-associated gene variants together than individuals with just one polymorphism.The highest OR was found for IL23R rs2201841 homozygous genotype with combination of positive CARD15 status(P<0.001,OR=9.15,95% CI:2.05-40.74). CONCLUSION:The present study suggests a cumulative effect of individual IBD susceptibility loci.展开更多
AIM:To study the inflammatory bowel disease-5 locus(IBD5)and interleukin-23 receptor(IL23R)gene variants in UC patients and test for gene-gene interaction.METHODS:The study population(n=625)was comprised of 320 unrela...AIM:To study the inflammatory bowel disease-5 locus(IBD5)and interleukin-23 receptor(IL23R)gene variants in UC patients and test for gene-gene interaction.METHODS:The study population(n=625)was comprised of 320 unrelated ulcerative colitis(UC)patients with Caucasian origin and 316 age-and gendermatched,healthy controls.Five variants in the IBD5 locus(IGR2198a_1 rs11739135,IGR2096a_1 rs12521868,IGR2230a_1 rs17622208,SLC22A4 rs1050152 and SLC22A5 rs2631367)and two of the IL23R gene(rs1004819,rs2201841)were analysed.PCR and restriction fragment length polymorphism methods were used for genotyping,the SLC22A4 rs1050152 genotypes were determined by direct sequencing.Interactions and specific genotype combinations of the seven variants were tested by binary logistic regression analysis.The IL23R genotypes were stratified by IBD5 genotypes for further interaction analyses.RESULTS:For the IL23R rs1004819 A allele we found significantly higher allele frequency(P=0.032)in UC patients compared to control subjects.The SNP rs1004819 showed significant association with UC risk for carriers(P=0.004,OR=1.606;95%CI:1.160-2.223)and the SNP rs2201841 for homozygotes(P=0.030,OR=1.983;95%CI:1.069-3.678).Individually none of the IBD5 markers conferred risk to UC development.There was no evidence for statistical interaction either between IBD5 loci and IL23R genes using logistic regression analysis.After genotype stratification,we could detect a positive association on the background of rs1004819 A allele for SLC22A4 T,SLC22A5 C,IGR2198a_1 C or IGR2096a_1 T allele,the highest OR was calculated in the presence of SLC22A4T allele(P=0.005,OR=2.015;95%CI:1.230-3.300).There was no association with UC for any combinations of rs1004819 and IGR2230a_1.The IL23R rs2201841homozygous genotype and IBD5 carrier status together did not confer susceptibility for UC.CONCLUSION:The present study has shown that UC susceptibility genes are likely to act in a complex interactive manner similar to CD.展开更多
基金Supported by The Grant of the Hungarian Science Foundation,No.OTKA K103983
文摘Rheumatoid arthritis(RA) is an autoimmune disease, resulting in a chronic, systemic inflammatory disorder. It may affect many tissues and organs, but it primarily affects the flexible joints. In clinical practice patient care generates many questions about diagnosis, prognosis, and treatment. It is challenging for health care specialists to keep up to date with the medical literature. This review summarizes the pathogenesis, the polymorphisms of interleukin and interleukin genes and the standard available and possible future immunologictargets for RA treatment. The identification of diseaseassociated interleukin and interleukin receptor genes can provide precious insight into the genetic variations prior to disease onset in order to identify the pathways important for RA pathogenesis. The knowledge of the complex genetic background may prove useful for developing novel therapies and making personalized medicine based on the individual's genetics.
基金Supported by The grant of the Hungarian Science Foundation,No.OTKA K103983
文摘Inflammatory bowel disease(IBD),which includes Crohn’s disease(CD)and ulcerative colitis(UC),represents a group of chronic inflammatory disorders caused by dysregulated immune responses in genetically predisposed individuals.Genetic markers are associated with disease phenotype and long-term evolution,but their value in everyday clinical practice is limited at the moment.IBD has a clear immunological background and interleukins play key role in the process.Almost130 original papers were revised including meta-analysis.It is clear these data are very important for understanding the base of the disease,especially in terms of clinical utility and validity,but text often do not available for the doctors use these in the clinical practice nowadays.We conducted a systematic review of the current literature on interleukin and interleukin receptor gene polymorphisms associated with IBD,performing an electronic search of PubMed Database from publications of the last 10 years,and used the following medical subject heading terms and/or text words:IBD,CD,UC,interleukins and polymorphisms.
基金Supported by the grant of Hungarian Science Foundation No. OTKA T 49589
文摘AIM: To investigate the frequency of the common NOD2/CARD15 susceptibility variants and two functional polymorphisms of OCTN cation transporter genes in Hungarian pediatric patients with Crohn’s disease (CD). METHODS: A cohort of 19 unrelated pediatric and 55 unrelated adult patients with Crohn’s disease and 49 healthy controls were studied. Genotyping of the three common CD-associated CARD15 variants (Arg702Trp, Gly908Arg and 1007finsC changes) with the SLC22A4 1672C→T, and SLC22A5 -207G→C mutations was performed by direct sequencing of the specifi c regions of these genes.RESULTS: At least one CARD15 mutation was present in 52.6% of the children and in 34.5% of the adults compared to 14.3% in controls. Surprisingly, strongly different mutation profi le was detected in the pediatric versus adult patients. While the G908R and 1007finsC variants were 18.4% and 21.1% in the pediatric group, they were 1.82% and 11.8% in the adults, and were 1.02% and 3.06% in the controls, respectively. The R702W allele was increased approximately two-fold in the adult subjects, while in the pediatric group it was only approximately 64% of the controls (9.09% in the adults, 2.63% in pediatric patients, and 4.08% in the controls). No accumulation of the OCTN variants was observed in any patient group versus the controls.CONCLUSION: The frequency of the NOD2/CARD15 susceptibility variants in the Hungarian pediatric CD population is high and the profile differs from the adult CD patients, whereas the results for SLC22A4 and SLC22A5 mutation screening do not confirm the assumption that the carriage of these genotypes means an obligatory susceptibility to CD.
基金Supported by The grant of the Hungarian Science Foundation,No.OTKA K103983
文摘Ulcerative colitis(UC) is one of the main types of inflammatory bowel disease, which is caused by dysregulated immune responses in genetically predisposed individuals. Several genetic factors, including interleukin and interleukin receptor gene polymorphisms and other inflammation-related genes play central role in mediating and modulating the inflammation in the human body, thereby these can be the main cause of development of the disease. It is clear these data are very important for understanding the base of the disease, especially in terms of clinical utility and validity, but summarized literature is exiguous for challenge health specialist that can used in the clinical practice nowadays. This review summarizes the current literature on inflammationrelated genetic polymorphisms which are associated with UC. We performed an electronic search of Pubmed Database among publications of the last 10 years, using the following medical subject heading terms: UC, ulcerative colitis, inflammation, genes, polymorphisms, and susceptibility.
基金Supported by the grants of Hungarian Science Foundation (OTKA T 0495X9)Hungarian Ministry of Health (ETT 497/2006)by the National Office for Research and Technology, "Pazmany Peter" program. (RET- II 08/2005)
基金Supportedby Hungarian Science Foundation(OTKA),No.K103983 and No.K119540
文摘AIM To investigate the association of seven single nucleotide polymorphisms(SNPs) of the IL23 R gene with the clinical picture of ulcerative colitis(UC). METHODS Genomic DNA samples of 131 patients (66 males, 65 females, mean age 55.4 ± 15.8 years) with Caucasian origin, diagnosed with UC were investigated. The diagnosis of UC was based on the established clinical, endoscopic, radiological, and histopathological guidelines. DNA was extracted from peripheral blood leukocytes by routine salting out method. Polymerase chain reaction and restriction fragment length polymorphism were used to identify the alleles of seven SNPs of IL23 R gene(rs11209026, rs10889677, rs1004819, rs2201841, rs7517847, rs10489629, rs7530511).RESULTS Four out of seven analyzed SNPs had statistically significant influence on the clinical picture of UC. Two SNPs were associated with greater colonic extension(rs2201841 P = 0.0084; rs10489629 P = 0.0405). For two of the SNPs, there was more frequently need for operations (rs2201841 P = 0.0348, OR = 8.0; rs10889677 P = 0.0347, OR = 8.0). The rs2201841 showed to be a risk factor for the development of iron deficiency (P = 0.0388, OR = 6.1837). For patients with the rs10889677, a therapy with azathioprine was more frequently necessary(P = 0.0116, OR = 6.1707). Patients with rs10489629 SNP had a lower risk for weight loss(P = 0.0169, OR = 0.3394). Carriers of the heterozygous variant had a higher risk for an extended disease (P = 0.0284). The rs7517847 showed a protective character leading to mild bowel movements. Three SNPs demonstrated no statistically significant influence on any examined clinical features of UC.CONCLUSION We demonstrated susceptible or protective character of the investigated IL23 R SNPs on the phenotype of UC, confirming the genetic association.
基金Supported by Grant of Hungarian Scientific Research Foundation,No.OTKA T 73430
文摘AIM:To investigate the interaction of interleukin-23 receptor(IL23R)(rs1004819 and rs2201841),autophagy-related 16-like 1(ATG16L1)(rs2241880), caspase recruitment domain-containing protein 15 (CARD15)genes,and IBD5 locus in Crohn's disease(CD) patients. METHODS:A total of 315 unrelated subjects with CD and 314 healthy controls were genotyped.Interactions and specific genotype combinations of a total of eight variants were tested.The variants of IBD5locus(IGR2198a_1 rs11739135 and IGR2096a_1 rs12521868),CARD15(R702W rs2066845 and L1007fs rs2066847),ATG16L1(rs2241880)and IL23R (rs1004819,rs2201841)genes were genotyped by PCR-RFLP,the G908R(rs2066844)in CARD15 was determined by direct sequencing. RESULTS:The association of ATG16L1 T300A with CD was confirmed[P=0.004,odds ratio(OR)=1.69, 95%CI:1.19-2.41],and both IL23R variants were found to represent significant risk for the disease(P= 0.008,OR=2.05,95%CI:1.20-3.50 for rs1004819 AA;P<0.001,OR=2.97,95%CI:1.65-5.33 for rs2201841 CC).Logistic regression analysis of pairwise interaction of the inflammatory bowel disease (IBD)loci indicated that IL23R,ATG16L1,CARD15 and IBD5(IGR2198a_1)contribute independently to disease risk.We also analysed the specific combina- tions by pair of individual ATG16L1,IL23R rs1004819, rs2201841,IGR2198a_1,IGR2096a_1 and CARD15 genotypes for disease risk influence.In almost all cases,the combined risk of susceptibility pairs was higher in patients carrying two different risk-associated gene variants together than individuals with just one polymorphism.The highest OR was found for IL23R rs2201841 homozygous genotype with combination of positive CARD15 status(P<0.001,OR=9.15,95% CI:2.05-40.74). CONCLUSION:The present study suggests a cumulative effect of individual IBD susceptibility loci.
基金Supported by The Grant of the Hungarian Science Foundation Nos.OTKA K103983 and T73430
文摘AIM:To study the inflammatory bowel disease-5 locus(IBD5)and interleukin-23 receptor(IL23R)gene variants in UC patients and test for gene-gene interaction.METHODS:The study population(n=625)was comprised of 320 unrelated ulcerative colitis(UC)patients with Caucasian origin and 316 age-and gendermatched,healthy controls.Five variants in the IBD5 locus(IGR2198a_1 rs11739135,IGR2096a_1 rs12521868,IGR2230a_1 rs17622208,SLC22A4 rs1050152 and SLC22A5 rs2631367)and two of the IL23R gene(rs1004819,rs2201841)were analysed.PCR and restriction fragment length polymorphism methods were used for genotyping,the SLC22A4 rs1050152 genotypes were determined by direct sequencing.Interactions and specific genotype combinations of the seven variants were tested by binary logistic regression analysis.The IL23R genotypes were stratified by IBD5 genotypes for further interaction analyses.RESULTS:For the IL23R rs1004819 A allele we found significantly higher allele frequency(P=0.032)in UC patients compared to control subjects.The SNP rs1004819 showed significant association with UC risk for carriers(P=0.004,OR=1.606;95%CI:1.160-2.223)and the SNP rs2201841 for homozygotes(P=0.030,OR=1.983;95%CI:1.069-3.678).Individually none of the IBD5 markers conferred risk to UC development.There was no evidence for statistical interaction either between IBD5 loci and IL23R genes using logistic regression analysis.After genotype stratification,we could detect a positive association on the background of rs1004819 A allele for SLC22A4 T,SLC22A5 C,IGR2198a_1 C or IGR2096a_1 T allele,the highest OR was calculated in the presence of SLC22A4T allele(P=0.005,OR=2.015;95%CI:1.230-3.300).There was no association with UC for any combinations of rs1004819 and IGR2230a_1.The IL23R rs2201841homozygous genotype and IBD5 carrier status together did not confer susceptibility for UC.CONCLUSION:The present study has shown that UC susceptibility genes are likely to act in a complex interactive manner similar to CD.