Down-Syndrome-Related Maternal Dysbiosis Might Be Triggered by Certain Classes of Antibiotics: A New Insight into the Possible Pathomechanisms.

Down syndrome (DS) is a leading human genomic abnormality resulting from the trisomy of chromosome 21. The genomic base of the aneuploidy behind this disease is complex, and this complexity poses formidable challenges to understanding the underlying molecular basis. In the spectrum of the classic DS risk factor associations, the role of nutrients, vitamins, and, in general, the foodborne-associated background, as part of the events ultimately leading to chromosome nondisjunction, has long been recognized as a well-established clinical association. The integrity of the microbiome is a basic condition in these events, and the dysbiosis may be associated with secondary health outcomes. The possible association of DS development with maternal gut microbiota should therefore require more attention. We have hypothesized that different classes of antibiotics might promote or inhibit the proliferation of different microbial taxa; and hence, we might find associations between the use of the different classes of antibiotics and the prevalence of DS through the modification of the microbiome. As antibiotics are considered major disruptors of the microbiome, it could be hypothesized that the consumption/exposure of certain classes of antibiotics might be associated with the prevalence of DS in European countries (N = 30). By utilizing three different statistical methods, comparisons have been made between the average yearly antibiotic consumption (1997-2020) and the estimated prevalence of people living with DS for the year 2019 as a percentage of the population in European countries. We have found strong statistical correlations between the consumption of tetracycline (J01A) and the narrow-spectrum, beta-lactamase-resistant penicillin (J01CF) and the prevalence of DS.

Characterization of Danube Swabian population samples on a high-resolution genome-wide basis.

BACKGROUND: German-derived ethnicities are one of the largest ethnic groups in Hungary, dating back to the formation of the Kingdom of Hungary, which took place at the beginning of the 11th century. Germans arrived in Hungary in many waves. The most significant immigration wave took place following the collapse of the Ottoman Empire in East-Central Europe which closed the 150 year long Ottoman occupation. To date, there are no comprehensive genome-wide studies investigating the genetic makeup of the Danube Swabians. Here we analyzed 47 Danube Swabian samples collected from elderly Swabian individuals living in the Dunaszekcso-Bár area, in Danube side villages of Southwest Hungary. These Swabians, according to self-declaration, did not admix with other ethnic groups for 3-6 succeeding generations. Using Illumina Infinium 720 K Beadchip genotype data, we applied allele frequency-based and haplotype-based genome-wide marker data analyses to investigate the ancestry and genetic composition of the collected Danube Swabian samples. RESULTS: Haplotype-based analyses like identity by descent segment analysis show that the investigated Danube Swabians possess significant German and other West European ancestry, but their Hungarian ancestry is also prominent. Our results suggest that their main source of ancestry can be traced back to Western Europe, presumably to the region of Germany. CONCLUSION: This is the first analysis of Danube Swabian population samples based on genome-wide autosomal data. Our results establish the basis for conducting further comprehensive research on Danube Swabians and on other German ethnicities of the Carpathian basin, which can help reconstruct their origin, and identify their major archaic genomic patterns.

Genome-Wide Marker Data-Based Comparative Population Analysis of Szeklers From Korond, Transylvania, and From Transylvania Living Non-Szekler Hungarians.

Genome-wide genotype data from 48 carefully selected population samples of Transylvania-living Szeklers and non-Szekler Hungarians were analyzed by comparative analysis. Our analyses involved contemporary Hungarians living in Hungary, other Europeans, and Eurasian samples counting 530 individuals altogether. The source of the Szekler samples was the commune of Korond, Transylvania. The analyzed non-Szekler Hungarian samples were collected from villages with a history dating back to the era of the Árpád Dynasty. Population structure by principal component analysis and ancestry analysis also revealed a great within-group similarity of the analyzed Szeklers and non-Szekler Transylvanian Hungarians. These groups also showed similar genetic patterns with each other. Haplotype analyses using identity-by-descent segment discovering tools showed that average pairwise identity-by-descent sharing is similar in the investigated populations, but the Korond Szekler samples had higher average sharing with the Hungarians from Hungary than non-Szekler Transylvanian Hungarians. Average sharing results showed that both groups are isolated compared to other Europeans, and pointed out that the non-Szekler Transylvanian Hungarian inhabitants of the investigated Árpád Age villages are more isolated than investigated Szeklers from Korond. This was confirmed by our autozygosity analysis as well. Identity-by-descent segment analyses and 4-population tests also confirmed that these Hungarian-speaking Transylvanian ethnic groups are strongly related to Hungarians living in Hungary.

Whole Exome Sequencing in a Series of Patients with a Clinical Diagnosis of Tuberous Sclerosis Not Confirmed by Targeted TSC1/TSC2 Sequencing.

BACKGROUND: Approximately fifteen percent of patients with tuberous sclerosis complex (TSC) phenotype do not have any genetic disease-causing mutations which could be responsible for the development of TSC. The lack of a proper diagnosis significantly affects the quality of life for these patients and their families. METHODS: The aim of our study was to use Whole Exome Sequencing (WES) in order to identify the genes responsible for the phenotype of nine patients with clinical signs of TSC, but without confirmed tuberous sclerosis complex 1/ tuberous sclerosis complex 2 (TSC1/TSC2) mutations using routine molecular genetic diagnostic tools. RESULTS: We found previously overlooked heterozygous nonsense mutations in TSC1, and a heterozygous intronic variant in TSC2. In one patient, two heterozygous missense variants were found in polycystic kidney and hepatic disease 1 (PKHD1), confirming polycystic kidney disease type 4. A heterozygous missense mutation in solute carrier family 12 member 5 (SLC12A5) was found in one patient, which is linked to cause susceptibility to idiopathic generalized epilepsy type 14. Heterozygous nonsense variant ring finger protein 213 (RNF213) was identified in one patient, which is associated with susceptibility to Moyamoya disease type 2. In the remaining three patients WES could not reveal any variants clinically relevant to the described phenotypes. CONCLUSION: Patients without appropriate diagnosis due to the lack of sensitivity of the currently used routine diagnostic methods can significantly profit from the wider application of next generation sequencing technologies in order to identify genes and variants responsible for their symptoms.

Age-Related Hearing Impairment Associated NAT2, GRM7, GRHL2 Susceptibility Gene Polymorphisms and Haplotypes in Roma and Hungarian Populations.

Age-related hearing impairment (ARHI) is the most frequent sensory disease in the elderly, which is caused by an interaction between genetic and environmental factors. Here we examined the ethnic differences, allele and genotype frequencies of the NAT2, GRM7, and GRHL2 genes pooled samples of healthy Hungarian and healthy and hearing impaired Roma people. Study populations of healthy Hungarian and Roma subjects were characterized for the rs1799930 NAT2, rs11928865 GRM7, rs10955255, rs13263539, and rs1981361 GRHL2 polymorphisms and deaf Roma subjects were characterized for the rs1799930 NAT2, rs13263539, and rs1981361 GRHL2 using a PCR-RFLP method. We found significant differences in minor allele frequencies for GRHL2 rs13263539 and rs1981361 polymorphism between healthy Roma and Hungarian samples (37.9% vs. 51.0% and 43.6% vs. 56.2%, respectively; p < 0.05). The differences of homozygous genotype of GRHL2 rs13263539 and rs1981361 variants, values were also significantly different (13.0% vs. 25.3% and 16.5 vs. 32.3%; p < 0.05). The NAT2 rs1799930 homozygous genotype was 14.0% in healthy Romas and 7.7% in Hungarians, while the minor A allele frequency was 38.0% and 26.7% in Roma and Hungarian population, respectively (p < 0.05). Furthermore, the frequency of GGT, GAC and GAT haplotypes was significantly higher in the Hungarian population than in healthy Roma (1.87 vs. 4.47%, 0.91 vs. 2.07% and 1.15 vs. 5.51%, respectively; p < 0.008). Present study revealed significant interethnic differences in allele polymorphisms of NAT2, GRM7 and GRHL2 exhibit quite marked ethnic differences in Roma populations that might have important implications for the preventive and therapeutic treatments in this population.

IL23R single nucleotide polymorphisms could be either beneficial or harmful in ulcerative colitis.

AIM: To investigate the association of seven single nucleotide polymorphisms (SNPs) of the IL23R 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 IL23R 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 IL23R SNPs on the phenotype of UC, confirming the genetic association.

Interethnic differences of cytochrome P450 gene polymorphisms may influence outcome of taxane therapy in Roma and Hungarian populations.

Taxanes are widely used microtubule-stabilizing chemotherapeutic agents in the treatment of cancers. Several cytochrome P450 gene variants have been proven to influence taxane metabolism and therapy. The purpose of this work was to determine the distribution of genetic variations of CYP1B1, CYP2C8 and CYP3A5 genes as the first report on taxane metabolizer cytochrome P450 gene polymorphisms in Roma and Hungarian populations. A total of 397 Roma and 412 Hungarian healthy subjects were genotyped for CYP1B1 c.4326C > G, CYP2C8 c.792C > G and CYP3A5 c.6986A > G variant alleles by PCR-RFLP assay and direct sequencing. We found significant differences in the frequencies of homozygous variant genotypes of CYP1B1 4326 GG (p = 0.002) and CYP3A5 6986 GG (p < 0.001) between Roma and Hungarian populations. Regarding minor allele frequencies, for CYP2C8 a significantly increased prevalence was found in 792G allele frequency in the Hungarian population compared to the Roma population (5.83% vs. 2.14%, p = 0.001). Our results can be used as possible predictive factors in population specific treatment algorithms to developing effective programs for a better outcome in patients treated with taxanes.

Increased prevalence of functional minor allele variants of drug metabolizing CYP2B6 and CYP2D6 genes in Roma population samples.

BACKGROUND: Cytochrome P450 2B6 and 2D6 are important enzymes in human drug metabolism. These phase I enzymes are known to contribute the biotransformation of clinically important pharmaceuticals, including antidepressants, anticancer and anxiolytic drugs. The aim of this work was to determine the pharmacogenetic profile of CYP2B6 and CYP2D6 in Roma and Hungarian population samples. METHODS: A study population of 426 healthy Roma and 431 healthy Hungarian subjects were characterized for CYP2B6 c.516G>T, CYP2D6 c.100C>T and c.1846G>A polymorphisms using predesigned TaqMan Drug Metabolism Genotyping Real Time-PCR assays. RESULTS: We found significant differences in the presence of CYP2B6 c.516G>T (p<0.001), CYP2D6 c.100C>T (p=0.003) and c.1846G>A (p=0.022) between Hungarian and Roma population. The 516T allele frequency was 33.6% in the Roma group, 21.4% in Hungarians, whereas the minor CYP2D6 100T allele was present in 26.6% in Romas and 20.5% in Hungarians. The 1864A allele frequency was 22.5% in Roma and 18.1% in Hungarian samples. A significant increase was found in genotype frequencies for homozygous minor allele carrier Roma participants compared to Hungarians for CYP2B6 516TT and CYP2D6 100TT. The following CYP2D6 genotypes were identified in Roma samples: *1/*1 (55.4%), *1/*4 (2.1%), *1/*10 (3.1%), *4/*10 (38.7%), *10/*10 (0.7%). CONCLUSION: Our results demonstrate an increased minor allele frequency for CYP2B6 and CYP2D6 polymorphisms in Roma samples that implies clinical significance in this ethnic group.

Extreme differences in SLCO1B3 functional polymorphisms in Roma and Hungarian populations.

Variants in SLCO1B3 transporter are linked to disposition and uptake of drugs and show high degree of heterogeneity between populations. A total of 467 Roma and 448 Hungarian subjects were genotyped for SLCO1B3 c.334T>G and c.1683-5676A>G variant alleles by PCR-RFLP assay and direct sequencing. We found significant differences in the frequencies of homozygous variant genotypes of SLCO1B3 334GG (41.54% vs. 8.04%, p<0.001) and 1683-5676GG (0.43% vs. 2.01%, p=0.028) between Romas and Hungarians. A significantly increased prevalence was found in SLCO1B3 1683-5676G allele frequency in Hungarians compared to the Roma population (15.07% vs. 3.43%, p≤0.001). The frequency of SLCO1B3 334G allele was significantly increased in Roma population compared to Hungarians (70.56% vs. 52.23%, p=0.001). The LD values between the examined SNPs were 80 and 90 in Roma and in Hungarian samples, respectively. Our results highlight notable pharmacogenetic differences between Roma and Hungarian populations, which may have therapeutic implications.

Functional variants of lipid level modifier MLXIPL, GCKR, GALNT2, CILP2, ANGPTL3 and TRIB1 genes in healthy Roma and Hungarian populations.

The role of triglyceride metabolism in different diseases, such as cardiovascular or cerebrovascular diseases is still under extensive investigations. In genome-wide studies several polymorphisms have been reported, which are highly associated with plasma lipid level changes. Our goal was to examine eight variants: rs12130333 at the ANGPTL3, rs16996148 at the CILP2, rs17321515 at the TRIB1, rs17145738 and rs3812316 of the MLXIPL, rs4846914 at GALNT2, rs1260326 and rs780094 residing at the GCKR loci. A total of 399 Roma (Gypsy) and 404 Hungarian population samples were genotyped using PCR-RFLP method. Significant differences were found between Roma and Hungarian population samples in both MLXIPL variants (C allele frequency of rs17145738: 94.1% vs. 85.6%, C allele frequency of rs3812316: 94.2% vs. 86.8% in Romas vs. in Hungarians, p < 0.05), in ANGPTL3 (T allele frequency of rs1213033: 12.2% vs. 18.5% in Romas vs. Hungarians, p < 0.05) and GALNT2 (G allele frequency of rs4846914: 46.6% vs. 54.5% Romas vs. in Hungarians, p < 0.05), while no differences over SNPs could be verified and the known minor alleles showed no correlation with triglyceride levels in any population samples. The current study revealed fundamental differences of known triglyceride modifying SNPs in Roma population. Failure of finding evidence for affected triglyceride metabolism shows that these susceptibility genes are much less effective compared for example to the apolipoprotein A5 gene.

Significant interethnic differencies in functional variants of PON1 and P2RY12 genes in Roma and Hungarian population samples.

Antiplatelet therapy with clopidogrel is one of the most common therapies given to patients worldwide. However, the clinical efficacy and toxicity of clopidogrel is not constant in every patient due to interindividual variations. There are several factors that contribute to these interindividual differencies such as SNPs in genes of specific receptors and enzymes. PON1 (paraoxonase 1) plays an important role in the bioactivation of clopidogrel. Single nucleotide polymorphisms of this gene decrease the activity of paraoxonase enzyme and lead to an unefficient clopidogrel effect. P2RY12 (purinergic receptor P2Y, G-protein coupled, 12) gene is coding a receptor, which is situated on the surface of the platelets and plays a role in ADP-induced platelet aggregation. In this study we investigated 2 functional SNPs of PON1 gene (rs662 and rs854560) and 3 variants of the P2RY12 gene (rs2046934, rs6798347, rs6801273) in samples pooled from average Hungarian Roma and Hungarian population samples with PCR-RFLP method. For the PON1 variants we detected that the R allele frequency was significantly lower in the Roma group compared to the Hungarian population. (0.249 vs 0.318 p < 0.001). By contrast, the frequency of the M allele was significantly higher in Roma than in Hungarians (0.332 vs 0.290 p < 0.05). For the 3 P2RY12 variants we could find significant differencies only in rs2046934: the frequency of the CC genotype is 7 times higher in Hungarians than in Romas (1.4 vs 0.2 %, p < 0.05). The data presented here represent a unique genetic profile in Roma people that has not been reported for other populations.

Genetic polymorphisms in promoter and intronic regions of CYP1A2 gene in Roma and Hungarian population samples.

The purpose of this study was to determine the interethnic differences of four CYP1A2 drug metabolizing enzyme variants. A total of 404 Roma and 396 Hungarian healthy subjects were genotyped for -163C>A, -729C>T, -2467delT and -3860G>A variants of CYP1A2 by RT-PCR and PCR-RFLP technique. The -3860A and -729T allele were not detectable in Roma samples, while in Hungarian samples were present with 2.02% and 0.25% prevalence, respectively. There was a 1.5-fold difference in presence of homozygous -163AA genotype between Hungarian and Roma samples (49.5% vs. 31.9%, p<0.001). The -163A allele frequency was 68.6% in Hungarians and 56.9% in Romas (p=0.025). The -2467delT allele frequency was 6.81% in Roma group and 5.81% in Hungarians. The most frequent allelic constellation was -3860G/-2467T/-729C/-163A in both populations. In conclusion, Hungarians have markedly elevated chance for rapid metabolism of CYP1A2 substrates, intensified procarcinogen activation and increased risk for cancers.

Interleukins and interleukin receptors in rheumatoid arthritis: Research, diagnostics and clinical implications.

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.

Admixture of beneficial and unfavourable variants of GLCCI1 and FCER2 in Roma samples can implicate different clinical response to corticosteroids.

Variants of glucocorticoid induced transcript 1 (GLCCI1) result decreased response to inhaled corticosteroids, while intronic variant of low-affinity IgE receptor (FCER2) is associated with exacerbation rates in children with asthma. We examined the ethnic differences, allele and genotype frequencies of two linked single nucleotide polymorphisms (rs37972, rs37973) of GLCCI1 and rs28364072 intronic variant of FCER2 gene in average Roma and Hungarian population. A study population of 474 healthy Roma and 397 Hungarian subjects were characterized for GLCCI1 and FCER2 polymorphisms using real time polymerase chain reaction (PCR) assay and PCR-restriction fragment length polymorphism method. The rs37972 and rs37973 polymorphisms in GLCCI1 were found in 100% linkage disequilibrium both in Romas and in Hungarians. We found significant differences between the two groups regarding both minor allele frequencies (54.5 vs. 43.8%, p ≤ 0.01) and homozygous genotype (31.6 vs. 21.3%, p ≤ 0.01) of GLCCI1. For FCER2 rs28364072 the homozygous variant genotype was present in 2.8% in Romas, while in Hungarians it was 5.8% (p = 0.032). The opposite changes of these two polymorphisms strongly suggest that contrary current belief analyses of GLCCI1 variants are insufficient for personalised glucocorticoid therapies in different populations.

Genetic update on inflammatory factors in ulcerative colitis: Review of the current literature.

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.

Interleukin and interleukin receptor gene polymorphisms in inflammatory bowel diseases susceptibility.

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.

Susceptibility to ulcerative colitis in Hungarian patients determined by gene-gene interactions.

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 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. 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 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. CONCLUSION: The present study has shown that UC susceptibility genes are likely to act in a complex interactive manner similar to CD.

Marked differences of haplotype tagging SNP distribution, linkage, and haplotype profile of IL23 receptor gene in Roma and Hungarian population samples.

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.

Difference of interleukin-23 receptor gene haplotype variants in ulcerative colitis compared to Crohn's disease and psoriasis.

OBJECTIVE: Polymorphisms of the interleukin-23 receptor (IL23R) gene have been found to play a role in the development of several autoimmune diseases. Our aim was to examine the possible effect of not only simple individual variants, but of haplotypes composed of them. SUBJECTS: We analysed 263 patients with psoriasis, 199 patients with Crohn's disease (CD), 282 patients with ulcerative colitis (UC), and 253 controls for rs1884444, rs11805303, rs7517847, rs2201841, rs10889677 and rs11209032 variants. METHODS: The genotypes were determined by using PCR/RFLP assay. Logistic regression analysis was used to compare the genotype distribution of the polymorphisms and haplotypes between the examined autoimmune diseases and healthy controls. RESULTS: Rs1884444 was found to confer risk for UC and psoriasis, rs10889677 for CD and psoriasis, while rs2201841 and rs7517847 had effect only in CD. Using these SNPs we could study the susceptibility haplotype profiles in these diseases with special attention to UC. Eight different haplotypes could be differentiated. We found that the SNPs exert their susceptibility character in specific haplotype blocks, and the frequency of one haplotype differed significantly in UC compared with both other diseases and also with healthy controls. This haplotype conferred risk for UC, even while it had a somewhat lower frequency in the other diseases than in controls. CONCLUSIONS: The data presented here serve as evidence for the need of haplotype analysis instead of just single standing SNP analysis when susceptibility is interpreted.