[Show abstract][Hide abstract] ABSTRACT: 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 immunologic targets for RA treatment. The identification of disease-associated 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.
World journal of orthopedics. 09/2014; 5(4):516-36.
[Show abstract][Hide abstract] ABSTRACT: 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 inflammation-related 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.
World journal of gastrointestinal pathophysiology. 08/2014; 5(3):304-21.
[Show abstract][Hide abstract] ABSTRACT: 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. Almost 130 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.
World Journal of Gastroenterology 03/2014; 20(12):3208-3222. · 2.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
The study population (n = 625) was comprised of 320 unrelated ulcerative colitis (UC) patients with Caucasian origin and 316 age- and gender-matched, 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.
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 SLC22A4 T 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 rs2201841 homozygous genotype and IBD5 carrier status together did not confer susceptibility for UC.
The present study has shown that UC susceptibility genes are likely to act in a complex interactive manner similar to CD.
World Journal of Gastroenterology 01/2014; 20(1):219-27. · 2.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Polymorphisms of the interleukin-23 receptor (IL23R) gene have been found to play an important role in the development of several autoimmune diseases. We examined five susceptible (rs10889677, rs1004819, rs2201841, rs11805303, rs11209032), one protective (rs7517847) and two neutral variants (rs7530511, rs1884444) of the IL23R gene in pooled DNA of healthy Roma (Gipsy) and Hungarian population samples. Our aim was to determine the genetic variability of the major haplotype tagging polymorphisms, and the haplotype profile of IL23R between the two groups. We analyzed 273 healthy Roma and 253 Hungarian DNA samples using PCR/RFLP assay. Comparing the five susceptible conferring alleles, there were significant increase (p<0.05), while in the protective alleles, there were decrease in the allele frequencies in Roma population (p<0.05). One of the neutral alleles showed increase, the another one did not differ between the two groups. The haplotype analysis of the SNPs revealed fundamentally different association types of SNPs in the two groups; moreover, the frequencies of the various haplotypes also exhibited strong differences, as of ht4 and ht5 haplotypes were significantly higher, whereas the frequencies of ht2 and ht3 haplotypes were significantly lower in the Roma population than in Hungarians (p<0.05). The data presented here show profound differences in the IL23R genetic profiles in the Roma population, that likely has also clinical implications in respect their possible role in the development of certain immunological diseases.
[Show abstract][Hide abstract] ABSTRACT: The IGR2198a_1 and IGR2096a_1 variants of the IBD5 region were found to be associated with Crohn's disease (CD) in the Hungarian population, while IGR2230a_1 does not seem to confer risk for the disease. In the present study, our aim was to investigate the statistical interaction of these three IBD5 polymorphisms with the +49 A/G substitution within the cytotoxic T lymphocyte antigen-4 (CTLA4) gene, detected previously as neutral gene variant in Hungarian IBD patients.
A total of 305 unrelated subjects with CD and 310 healthy controls were genotyped with PCR-RFLP methods.
In contrast with single gene effects, after genotype stratification, the IGR2198a_1 C and IGR2096a_1 T variants were found to confer susceptibility only in subjects with CTLA4 +49 AA genotype (P = 0.008; OR = 1.86 and P = 0.016; OR = 1.74, respectively), for IGR2230a_1 no such effect on disease risk could be demonstrated.
Analysis of specific genotype combinations unfolded a possible association between the CTLA4 +49 A/G substitution and two of the observed IBD5 variants with respect to disease risk.
International Journal of Colorectal Disease 04/2011; 26(9):1119-25. · 2.24 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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 IBD5 locus (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.
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 combinations 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).
The present study suggests a cumulative effect of individual IBD susceptibility loci.
World Journal of Gastroenterology 01/2010; 16(2):176-83. · 2.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The IBD5 locus (MIM#606348) on chromosome 5q31 has been demonstrated to confer increased risk for inflammatory bowel disease. Controversial reports have been published about the significance of individual loci located in this region. Here we investigated the possible genetic association of inflammatory bowel diseases with C1672T of SLC22A4 and G-207C SLC22A5 alleles, and with IGR2096a_1 (rs12521868) and IGR2198a_1 (rs11739135) susceptibility variants of the IBD5 region located on chromosome 5q31.
Total of 440 patients, 206 with Crohn's disease, 234 with ulcerative colitis, and 279 controls were studied by PCR-RFLP methods.
Neither the C1672T, and G-207C alleles, nor the TC haplotype were found to confer risk for Crohn's disease or ulcerative colitis. By contrast, both of the minor allele frequencies of IGR2096a_1 T (48.1%) and IGR2198a_1 C (46.1%) were increased in Crohn's disease subjects as compared with the controls (38.5% and 38.4%, respectively; p<0.05). Using regression analysis adjusted to age and gender these alleles were found to confer risk for Crohn's disease (OR=1.694, 95% CI: 1.137-2.522; p=0.010 for T allele, OR=1.644, 95% CI=1.103-2.449; p=0.015 for C allele of IGRs). In UC no such associations were found.
Our results revealed the susceptibility nature of the examined IGR minor alleles in Hungarians, which nation differs historically from the surrounding Caucasian populations in origin of the founders of the state.
[Show abstract][Hide abstract] ABSTRACT: We investigated the possible association of IBD with C1672T of SLC22A4 and G-207C of SLC22A5 alleles, and with the novel IGR2096a_1 (rs12521868) and IGR2198a_1 (rs11739135) susceptibility loci, all located on IBD5 locus of chromosome 5q31.
DNA of 217 Crohn's disease, 252 ulcerative colitis, and 290 control patients were analyzed by polymerase chain reaction/restriction fragment length polymorphism methods.
Neither the C1672T and G-207C alleles, nor the TC haplotype were found to be risk factors. By contrast, the minor allele frequencies of IGR2096a_1 T (47.2%) and IGR2198a_1 C (45.9%) were increased in Crohn's disease compared with the controls (38.2% and 37.7%, respectively; p < 0.05); multivariate regression analysis revealed a risk nature for Crohn's disease (OR = 1.748, 95% CI 1.186-2.574; p = 0.007 for T allele, OR = 1.646, 95% CI 1.119-2.423, p = 0.011 for C allele of IGRs).
The data suggest a special haplotype arrangement of susceptibility genes at the IBD5 locus in Hungarians, which nation differs historically from the surrounding Caucasian ethnicities in its origin.
International Journal of Colorectal Disease 02/2009; 24(5):503-7. · 2.24 Impact Factor