The importance of genetic factors in the development of celiac disease in children of the Uzbek population

The results of genetic studies have proven the relationship of celiac disease with class II genes of the major histocompatibility complex (HLA), in particular with the DQ locus. The presence of specific alleles at the HLA-DQ locus is necessary, but insufficient, for the realization of the disease phenotype. In Uzbekistan, the distribution of HLA markers in children with celiac disease has not been studied and these studies are required. Purpose — to establish the peculiarities of the distribution of HLA II class celiac disease alleles in children in the Uzbek population. Materials and methods. We examined 54 children with celiac disease of the Uzbek population, who were registered and receiving inpatient treatment at the Republican Specialized Scientific and Practical Medical Center of Pediatrics. The age of the examined children was from 1 to 14 years old, the average age was 7.3±1.9 years. The control group consisted of 109 unrelated Uzbeks without immune diseases. Molecular typing of HLA II class genes was determined by DNA chain reaction polymerase. Results. As a result of gene typing, 48 (88.8%) out of 54 investigated had DQ2 and DQ8 haplotypes associated with celiac disease. Haplotypes with only DQ2 and DQ8 were found in 19 (39.5%) and 7 (14.5%), respectively. DQ2 from 48 children was found in 18 (37.5%) children in the trans-position, in 2 (4,1%) — as two copies of DQ2 dimers, and in 1 (2%) case in combination with DQ8. Only in one case (2%) was DQ8 found as two copies of DQ8 dimers. The frequency of occurrence of the HLA-DRB1*07 and *13 alleles was significantly higher than in the control group. The maximum value of the relative risk and the criterion of reliability are noted in the DQA1*0501 allele, i.e. it is positively associated with celiac disease (χ2=7.28, RR=2.03). Significance criterion and relative risk were observed in sick children with DQB1*0201 (χ2=6.74, RR=1.97) associated with celiac disease. The number of haplotype (DQA1*0501-DQB1*0201) was 36 (75%). Conclusions. A specific predisposition to celiac disease in children of the Uzbek population is associated with the genes HLA-DQA1*0501, HLA-DQB1*0201, HLA-DRB1*07 and *13. Alleles such as DRB1*15, DQA1*0102, DQB1*0303 and *0502, have a protective effect in the development of celiac disease in children of the Uzbek population. A high frequency of carriage of the DRB1*13 — HLA-DQА1*0501 and DQB1*0201 (DQ2 type) haplotype in Uzbeks (75%) was found, which requires a more thorough population genetic study of the Uzbek population for the HLA II class DRB1-DQA1-DQB1 genes. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of these Institutes. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the authors. Key words: celiac disease, children, genetics, HLA class II.

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THE PREVALENCE OF CELIAC DISEASE AMONG PATIENTS WITH FAMILIAL MEDITERRANEAN FEVER

Arquivos de Gastroenterologia ◽

10.1590/s0004-28032015000100012 ◽

2015 ◽

Vol 52 (1) ◽

pp. 55-58 ◽

Cited By ~ 2

Author(s):

Sedat IŞIKAY ◽

Nurgül IŞIKAY ◽

Halil KOCAMAZ

Keyword(s):

Celiac Disease ◽

Familial Mediterranean Fever ◽

Tissue Transglutaminase ◽

Control Group ◽

Marsh Type ◽

Significant Difference ◽

Healthy Control ◽

Mediterranean Fever ◽

Relationship Of ◽

The Relationship

Background Familial Mediterranean Fever and celiac disease are both related to auto-inflammation and/or auto-immunity and they share some common clinical features such as abdominal pain, diarrhea, bloating and flatulence. Objectives We aimed to determine the association of these two diseases, if present. Methods Totally 112 patients diagnosed with Familial Mediterranean Fever and 32 cases as healthy control were included in the study. All participants were examined for the evidence of celiac disease, with serum tissue transglutaminase IgA levels (tTG IgA). Results Totally 144 cases, 112 with Familial Mediterranean Fever and 32 healthy control cases were included in the study. tTG IgA positivity was determined in three cases with Familial Mediterranean Fever and in one case in control group. In that aspect there was no significant difference regarding the tTG IgA positivity between groups (P=0.81). Duodenum biopsy was performed to the tTG IgA positive cases and revealed Marsh Type 3b in two Familial Mediterranean Fever cases and Marsh Type 3c in the other one while the biopsy results were of the only tTG IgA positive case in control group was Marsh Type 3b. In HLA evaluation of the celiac cases; HLA DQ2 was present in two celiac cases of the Familial Mediterranean Fever group and in the only celiac case of the control group while HLA DQ8 was present in one celiac case of the Familial Mediterranean Fever group. Conclusions We did not determine an association of Familial Mediterranean Fever with celiac disease. Larger studies with subgroup analysis are warranted to determine the relationship of these two diseases.

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Celiac disease risk stratification based on HLA-DQ heterodimer (HLA-DQA1 ~ DQB1) typing in a large cohort of adults with suspected celiac disease

Human Immunology ◽

10.1016/j.humimm.2020.01.006 ◽

2020 ◽

Vol 81 (2-3) ◽

pp. 59-64 ◽

Cited By ~ 1

Author(s):

Rok Seon Choung ◽

John R. Mills ◽

Melissa R. Snyder ◽

Joseph A. Murray ◽

Manish J. Gandhi

Keyword(s):

Celiac Disease ◽

Risk Stratification ◽

Disease Risk ◽

Large Cohort ◽

Hla Dq ◽

Hla Dqa1

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Evidence for a primary association of celiac disease to a particular HLA-DQ alpha/beta heterodimer.

Journal of Experimental Medicine ◽

10.1084/jem.169.1.345 ◽

1989 ◽

Vol 169 (1) ◽

pp. 345-350 ◽

Cited By ~ 623

Author(s):

L M Sollid ◽

G Markussen ◽

J Ek ◽

H Gjerde ◽

F Vartdal ◽

...

Keyword(s):

Celiac Disease ◽

Oligonucleotide Probes ◽

Hla Dq ◽

Allele Specific ◽

In Trans ◽

Dqb1 Gene ◽

Alpha Beta ◽

Hla Dqa1 ◽

In Cis ◽

Dqb1 Allele

Typing of DNA from 94 unrelated children with celiac disease (CD) with HLA-DQA1 and -DQB1 allele-specific oligonucleotide probes revealed that all but one (i.e., 98.9%) may share a particular combination of a DQA1 and a DQB1 gene. These genes are arranged in cis position on the DR3DQw2 haplotype and in trans position in DR5DQw7/DR7DQw2 heterozygous individuals. Thus, most CD patients may share the same cis- or trans-encoded HLA-DQ alpha/beta heterodimer.

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Determination of High-Resolution HLA-DQB1 Suballeles and IL-17 Polymorphisms in Turkish Pediatric Patients

Journal of Pediatric Genetics ◽

10.1055/s-0041-1722856 ◽

2021 ◽

Author(s):

Aslı Eldem ◽

Tülay Kılıçaslan Ayna ◽

Maşallah Baran ◽

Mustafa Soyöz ◽

İbrahim Pirim

Keyword(s):

High Resolution ◽

Patient Group ◽

Human Leukocyte ◽

Control Group ◽

Related Factor ◽

Genotype Frequencies ◽

Restriction Fragment Polymorphism ◽

Hla Dq ◽

Hla Dqa1 ◽

And Control

AbstractCeliac disease (CD) is an autoimmune enteropathy in the small intestine caused by gluten intolerance of the patients. The most important genetic disease-related factor is human leukocyte antigen (HLA)-DQ polymorphism. Association between interleukin (IL)-17A expression of CD4+ T cells and various autoimmune diseases has been reported. The aim of this study was to investigate the relationship between single nucleotide polymorphism (rs2275913) IL-17A and HLA-DQ polymorphisms in Turkish pediatric celiac patients. Study group included 125 pediatric celiac patients with CD and 100 healthy pediatric controls. Deoxyribonucleic acid was isolated from peripheral blood samples. IL-17A polymorphism (rs2275913) was analyzed by polymerase chain reaction-restriction fragment polymorphism method. IL-17A polymorphism and low-/high-resolution HLA-DQ results of patients were evaluated. GG and GA genotype frequencies of IL-17A (rs2275913) polymorphism were significantly higher (p < 0.05) in the CD patients than the control group. HLA-DQB1*02 and HLA-DQA1*05 alleles were detected in patients, while HLA-DQB1*03 and HLA-DQA1*01 alleles in the control group. Also, when we compared the patient and control groups in terms of HLA-DQ-DR haplotypes, HLA-DQB1*02-DQA1*05-DRB1*03 was found with the relative risk of 42.5 (p < 0.05). As a result of high-resolution HLA-DQB1 typing, DQB1*02:01 and DQB1*03:02 were at high frequency (p < 0.05; in 25 patient group). IL-17A (rs2275913) polymorphism genotype frequency was found to be significant in the patient group compared with the control group. The most common HLA-DQB1 suballele was observed as DQB1*02:01.

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231-P: Relative risk of celiac disease based on HLA-DQA1 and HLA-DQB1 genotypes

Human Immunology ◽

10.1016/j.humimm.2009.09.264 ◽

2009 ◽

Vol 70 ◽

pp. S128

Author(s):

Curt Lind ◽

Priyanka Chugh ◽

Sara Fontanez ◽

Patricia Bierly ◽

Ritu Verma ◽

...

Keyword(s):

Celiac Disease ◽

Relative Risk ◽

Hla Dqa1

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Tristetraprolin/ZFP36 regulates the turnover of autoimmune-associated HLA-DQ mRNAs

10.1101/337907 ◽

2018 ◽

Author(s):

Laura Pisapia ◽

Russell S. Hamilton ◽

Federica Farina ◽

Vito D’Agostino ◽

Pasquale Barba ◽

...

Keyword(s):

Celiac Disease ◽

Rna Binding ◽

Zinc Finger Protein ◽

Rna Binding Proteins ◽

Autoimmune Response ◽

Affinity Binding ◽

Hla Dq ◽

Rnp Complex ◽

Protein Components ◽

Hla Dqa1

AbstractWe have previously demonstrated that the expression of HLA class II genes is regulated by the binding of a ribonucleoprotein complex that affects the mRNA processing. We identified protein components of a complex binding transcripts encoding the HLA-DR molecule. Here we investigate whether the same RNA binding proteins interact with 3’UTR of mRNAs encoding the HLA-DQ isotype. Specifically, we focused on the HLA-DQ2.5 molecule, expressed on the surface of antigen presenting cells, and representing the main susceptibility factor for celiac disease (CD). This molecule, encoded by HLA-DQA1*05 and HLA-DQB1*02 alleles, presents the antigenic gluten peptides to CD4+ T lymphocytes, activating the autoimmune response.Here, we identified an additional component of the RNP complex, Tristetraprolin (TTP) or ZFP36, a zinc-finger protein, widely described as a factor modulating mRNA stability. TTP shows high affinity binding to 3’UTR of CD-associated HLA-DQA1*05 and HLA-DQB1*02 alleles, in contrast to lower affinity binding to HLA-DQA1*01 and HLA-DQB1*05 non-CD associated alleles. Our in silico analysis, confirmed by molecular experiments, demonstrates that TTP specifically modulates the stability of the transcripts associated with celiac disease.

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Investigating class II HLA antigens' association with insulin-dependent diabetes mellitus in population of Vojvodina

Medicinski pregled ◽

10.2298/mpns0302026v ◽

2003 ◽

Vol 56 (1-2) ◽

pp. 26-31

Author(s):

Svetlana Vojvodic

Keyword(s):

Diabetes Mellitus ◽

Relative Risk ◽

Hla Antigens ◽

Insulin Dependent Diabetes Mellitus ◽

Class Ii ◽

Insulin Dependent Diabetes ◽

Dependent Diabetes Mellitus ◽

Control Group ◽

Significant Difference ◽

Insulin Dependent

Introduction Class II HLA antigens were investigated in a group of 28 patients with insulin-dependent diabetes mellitus (IDDM) and 218 healthy unrelated persons (control group) from Vojvodina. Material and methods We used a modified two-colour immunofluorescence method (serologic technique) to determine the phenotype of DR and DQ locus HLA antigens. Phenotype frequencies of class II HLA antigens were determined in both investigated groups and were used for calculating relative risk (RR). If RR was higher than 1, we calculated the population attributable risk (EF), and if RR was lower than 1, we calculated the preventive fraction (PF). Investigation of statistically significant differences in frequencies of class II HLA antigens in patients and control group was performed by using ?2 test. Results Results of investigation showed that values of RR were higher than 1 for HLA DR4 (2,808), DR10 (1,116) and DQ3 (1,386), while we noticed a statistically significant difference in frequencies of HLA DR4 (?2 test: 4,805) in patients regarding control group. HLA DQ1 antigen has a preventive role in development of IDDM due to highest value of PF (0,314). Conclusion Results of our investigation confirm that there is an association of HLA DR4 with IDDM in population of Vojvodina. High values of relative risk of IDDM, noticed in persons with HLA DR4 antigen, point to the degree of risk of IDDM, which is a disease with great socioeconomic importance in Vojvodina.

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HLA-DQA1 and HLA-DQB1 Alleles, Conferring Susceptibility to Celiac Disease and Type 1 Diabetes, are More Expressed Than Non-Predisposing Alleles and are Coordinately Regulated

Cells ◽

10.3390/cells8070751 ◽

2019 ◽

Vol 8 (7) ◽

pp. 751 ◽

Cited By ~ 11

Author(s):

Farina ◽

Picascia ◽

Pisapia ◽

Barba ◽

Vitale ◽

...

Keyword(s):

T Cells ◽

Type 1 Diabetes ◽

Celiac Disease ◽

Cd4 T Cells ◽

High Expression ◽

Transcriptional Level ◽

Risk Alleles ◽

Hla Dq ◽

Hla Dqa1

HLA DQA1*05 and DQB1*02 alleles encoding the DQ2.5 molecule and HLA DQA1*03 and DQB1*03 alleles encoding DQ8 molecules are strongly associated with celiac disease (CD) and type 1 diabetes (T1D), two common autoimmune diseases (AD). We previously demonstrated that DQ2.5 genes showed a higher expression with respect to non-CD associated alleles in heterozygous DQ2.5 positive (HLA DR1/DR3) antigen presenting cells (APC) of CD patients. This differential expression affected the level of the encoded DQ2.5 molecules on the APC surface and established the strength of gluten-specific CD4+ T cells response. Here, we expanded the expression analysis of risk alleles in patients affected by T1D or by T1D and CD comorbidity. In agreement with previous findings, we found that DQ2.5 and DQ8 risk alleles are more expressed than non-associated alleles also in T1D patients and favor the self-antigen presentation. To investigate the mechanism causing the high expression of risk alleles, we focused on HLA DQA1*05 and DQB1*02 alleles and, by ectopic expression of a single mRNA, we modified the quantitative equilibrium among the two transcripts. After transfection of DR7/DR14 B-LCL with HLA-DQA1*05 cDNA, we observed an overexpression of the endogenous DQB1*02 allele. The DQ2.5 heterodimer synthesized was functional and able to present gluten antigens to cognate CD4+ T cells. Our results indicated that the high expression of alpha and beta transcripts, encoding for the DQ2.5 heterodimeric molecules, was strictly coordinated by a mechanism acting at a transcriptional level. These findings suggested that, in addition to the predisposing HLA-DQ genotype, also the expression of risk alleles contributed to the establishment of autoimmunity.

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Prevalence of HLA DQ 2, 8 in children with celiac disease

Human Antibodies ◽

10.3233/hab-200437 ◽

2021 ◽

pp. 1-6

Author(s):

Seyed Mohsen Dehghani ◽

Naqi Dara ◽

Behrooz Gharesifar ◽

Iraj Shahramian ◽

Fatemeh Dalili ◽

...

Keyword(s):

Celiac Disease ◽

Normal Population ◽

Failure To Thrive ◽

Hla Typing ◽

Control Group ◽

P Value ◽

Normal Children ◽

Hla Dq ◽

Inducing Factors ◽

Hla Dq2

OBJECTIVE: Celiac disease is a chronic disease that affect small bowel by making its villi become atrophic. Various environmental and genetic factors have been identify as inducing factors for celiac disease. Most of the patients has one of the HLA DQ forms. Although the prevalence of these genes are variable in different areas of the world, we do not have a comprehensive information about this issue in our region. Thus the aim of present study is to investigate the prevalence of HLA DQ typing of patients who visited Emam Reza Gastroenterology clinic of Shiraz(IRAN). METHODS: In this case-control study all under 18 years old children who were diagnosed with celiac disease and have visited Emam Reza gastroenterology clinic were investigated. The diagnosis of celiac disease was made by history, physical exam, serologic test, and histopathology of duodenal biopsy. Blood sample was taken and HLA typing performed using PCR method at Motahari clinic cytology laboratory. Also those people who neither them self nor their first degree relatives were not case of celiac disease and underwent HLA typing for other reason were identified as control group. The statistical analysis was done using SPSS 18 software. The p value < 0.05 was identified as statistically significant. RESULTS: A total of 139 patients with celiac disease and 146 normal children were studied. The mean age of the patient with celiac disease were 9.1 years old with standard deviation of 3.4 years old. 64% of the celiac patients were girls and 36% were boys. While this proportion was 54.4% for boy and 48.6% for girls in control group. The most common HLA in celiac patients group were HLA DQ2 and 8 but the most common ones in control group were HLA DQ 8 and 5. Failure to Thrive were the most common signs of the celiac patients with a prevalence of 60 children. Total IgA titer were normal in 98.6% of the patients and TTG IgA titer were positive in 93.5% of the patients. The most common co existing disease with the celiac disease were diabetes with a prevalence of 30 children (66.7%). CONCLUSION: present study reveals that the prevalence of the HLA DQ2 and 8 among patients with celiac disease is 72.6% and 53% in our normal population.

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The Association of Myasthenia Gravis with HLA class II Antigens in Iraqi Patients

Baghdad Science Journal ◽

10.21123/bsj.10.1.126-132 ◽

2013 ◽

Vol 10 (1) ◽

pp. 126-132

Author(s):

Baghdad Science Journal

Keyword(s):

Myasthenia Gravis ◽

Class Ii ◽

Hla Class Ii ◽

Control Group ◽

P Value ◽

Hla Dq ◽

Healthy Control ◽

Hla Dr3 ◽

Class Ii Antigens ◽

Hla Dq2

The nature and intensity of the association of myasthenia gravis (MG) with distinct human leukocyte antigen (HLA) haplotypes differ between ethnic populations, so this study determined the association of HLA class II antigens with myasthenia gravis (MG) in Iraq.The study included Iraqi patients diagnosed with MG and two control groups the first of 54 insulin dependent diabetes mellitus patients and the second of 237 subjects as a normal control group. The test used was microlymphocytotoxicity test.The work was done in the Teaching Laboratories/Medical City/Baghdad.Results: positive associations were observed (etiological risk factors) as follows: 1. HLA-DR locus showed one positively associated allele when compared to healthy control and this was HLA-DR3 (RR: 21.05, EF0.73, & P value ? 0.05), While when compared to IDDM control no significant association appeared (since the same allele is positively associated with IDDM). 2. HLA-DQ locus showed only one positively associated allele when compared to healthy control; this was HLA-DQ2 (RR 4.67, EF 0.50, and P value ? 0.05). While no significant association appeared when compared to IDDM control. Other important clinical association were observed; association with age, gender, strong stressful events, thymoma, and other autoimmune disorders. Conclusion: The positively associated antigens which were found as follows HLA-DR3 and HLA-DQ2, while no negative association was detected.

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