Skip to main content
Top
Published in: BMC Gastroenterology 1/2018

Open Access 01-12-2018 | Research article

HLA-DQ2 and -DQ8 genotype frequency in Syrian celiac disease children: HLA-DQ relative risks evaluation

Authors: Hossam Murad, Batoul Jazairi, Issam Khansaa, Doaa Olabi, Lina Khouri

Published in: BMC Gastroenterology | Issue 1/2018

Login to get access

Abstract

Background

Celiac disease (CD) is a common autoimmune disease in Syria which manifesting with inflammation of the small intestine and with various extra intestinal symptoms. The disease is associated with human HLA-DQ genes encoding HLA-DQ2 and DQ8 proteins.

Methods

In this study, 49 children patients of CD and 58 healthy control samples were genotyped for HLA-DQ genes using SSP-PCR technique. Relative risks for different genotypes were also evaluated.

Results

The DQB1*0201 allele was the most common in the patients (77.6%) followed by DQB1*0302 allele (10.2%). The highest HLA-DQB risk for CD development was found in patients carriers a DQ2.5/DQ8 genotype (1/10), followed by the patients carriers DQ2.5/DQ2.5 (1/12).

Conclusion

The significant differences in the frequency of HLA-DQ2 and HLA-DQ8 in Syrian patients in compared with controls and relative risks predicted demonstrated the importance role of these alleles in the development of CD in Syrian children patients.
Literature
1.
go back to reference Kurppa K, Taavela J, Saavalainen P, Kaukinen K, Lindfors K. Novel diagnostic techniques for celiac disease. Expert Rev Gastroenterol Hepatol. 2016;10:795–805.CrossRefPubMed Kurppa K, Taavela J, Saavalainen P, Kaukinen K, Lindfors K. Novel diagnostic techniques for celiac disease. Expert Rev Gastroenterol Hepatol. 2016;10:795–805.CrossRefPubMed
2.
go back to reference Holopainen P. Genetic susceptibility to celiac disease: HLA-unlinked candidate genes: University of Helsinki, Faculty of Science, Department of Biosciences. Helsinki: 2005. Holopainen P. Genetic susceptibility to celiac disease: HLA-unlinked candidate genes: University of Helsinki, Faculty of Science, Department of Biosciences. Helsinki: 2005.
3.
go back to reference Villanacci V, Ceppa P, Tavani E, Vindigni C, Volta U. Coeliac disease: the histology report. Dig Liver Dis. 2011;43(Suppl 4):S385–95.CrossRefPubMed Villanacci V, Ceppa P, Tavani E, Vindigni C, Volta U. Coeliac disease: the histology report. Dig Liver Dis. 2011;43(Suppl 4):S385–95.CrossRefPubMed
4.
go back to reference Tucci F, Astarita L, Abkari A, Abu-Zekry M, Attard T, Ben Hariz M, Bilbao JR, Boudraa G, Boukthir S, Costa S, et al. Celiac disease in the Mediterranean area. BMC Gastroenterol. 2014;14:24.CrossRefPubMedPubMedCentral Tucci F, Astarita L, Abkari A, Abu-Zekry M, Attard T, Ben Hariz M, Bilbao JR, Boudraa G, Boukthir S, Costa S, et al. Celiac disease in the Mediterranean area. BMC Gastroenterol. 2014;14:24.CrossRefPubMedPubMedCentral
5.
go back to reference Greco L, Timpone L, Abkari A, Abu-Zekry M, Attard T, Bouguerra F, Cullufi P, Kansu A, Micetic-Turk D, Misak Z, et al. Burden of celiac disease in the Mediterranean area. World J Gastroenterol. 2011;17:4971–8.CrossRefPubMedPubMedCentral Greco L, Timpone L, Abkari A, Abu-Zekry M, Attard T, Bouguerra F, Cullufi P, Kansu A, Micetic-Turk D, Misak Z, et al. Burden of celiac disease in the Mediterranean area. World J Gastroenterol. 2011;17:4971–8.CrossRefPubMedPubMedCentral
6.
7.
go back to reference Schuppan D, Junker Y, Barisani D. Celiac disease: from pathogenesis to novel therapies. Gastroenterology. 2009;137:1912–33.CrossRefPubMed Schuppan D, Junker Y, Barisani D. Celiac disease: from pathogenesis to novel therapies. Gastroenterology. 2009;137:1912–33.CrossRefPubMed
8.
go back to reference Green PH, Lebwohl B, Greywoode R. Celiac disease. J Allergy Clin Immunol. 2015;135:1099–106. quiz 1107CrossRefPubMed Green PH, Lebwohl B, Greywoode R. Celiac disease. J Allergy Clin Immunol. 2015;135:1099–106. quiz 1107CrossRefPubMed
9.
go back to reference Sollid LM. The roles of MHC class II genes and post-translational modification in celiac disease. Immunogenetics. 2017;69:605–16.CrossRefPubMed Sollid LM. The roles of MHC class II genes and post-translational modification in celiac disease. Immunogenetics. 2017;69:605–16.CrossRefPubMed
10.
go back to reference Romanos J, Wijmenga C. Predicting susceptibility to celiac disease by genetic risk profiling. Ann Gastroenterol Hepatol. 2010;1(1):1–8. Romanos J, Wijmenga C. Predicting susceptibility to celiac disease by genetic risk profiling. Ann Gastroenterol Hepatol. 2010;1(1):1–8.
11.
go back to reference Fallang LE, Bergseng E, Hotta K, Berg-Larsen A, Kim CY, Sollid LM. Differences in the risk of celiac disease associated with HLA-DQ2.5 or HLA-DQ2.2 are related to sustained gluten antigen presentation. Nat Immunol. 2009;10:1096–101.CrossRefPubMed Fallang LE, Bergseng E, Hotta K, Berg-Larsen A, Kim CY, Sollid LM. Differences in the risk of celiac disease associated with HLA-DQ2.5 or HLA-DQ2.2 are related to sustained gluten antigen presentation. Nat Immunol. 2009;10:1096–101.CrossRefPubMed
12.
go back to reference Vader W, Stepniak D, Kooy Y, Mearin L, Thompson A, van Rood JJ, Spaenij L, Koning F. The HLA-DQ2 gene dose effect in celiac disease is directly related to the magnitude and breadth of gluten-specific T cell responses. Proc Natl Acad Sci U S A. 2003;100:12390–5.CrossRefPubMedPubMedCentral Vader W, Stepniak D, Kooy Y, Mearin L, Thompson A, van Rood JJ, Spaenij L, Koning F. The HLA-DQ2 gene dose effect in celiac disease is directly related to the magnitude and breadth of gluten-specific T cell responses. Proc Natl Acad Sci U S A. 2003;100:12390–5.CrossRefPubMedPubMedCentral
13.
go back to reference Congia M, Cucca F, Frau F, Lampis R, Melis L, Clemente MG, Cao A, De Virgiliis SA. Gene dosage effect of the DQA1*0501/DQB1*0201 allelic combination influences the clinical heterogeneity of celiac disease. Hum Immunol. 1994;40:138–42.CrossRefPubMed Congia M, Cucca F, Frau F, Lampis R, Melis L, Clemente MG, Cao A, De Virgiliis SA. Gene dosage effect of the DQA1*0501/DQB1*0201 allelic combination influences the clinical heterogeneity of celiac disease. Hum Immunol. 1994;40:138–42.CrossRefPubMed
14.
go back to reference Husby S, Koletzko S, Korponay-Szabo IR, Mearin ML, Phillips A, Shamir R, Troncone R, Giersiepen K, Branski D, Catassi C, et al. European Society for Pediatric Gastroenterology, hepatology, and nutrition guidelines for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr. 2012;54:136–60.CrossRefPubMed Husby S, Koletzko S, Korponay-Szabo IR, Mearin ML, Phillips A, Shamir R, Troncone R, Giersiepen K, Branski D, Catassi C, et al. European Society for Pediatric Gastroenterology, hepatology, and nutrition guidelines for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr. 2012;54:136–60.CrossRefPubMed
15.
go back to reference Ribes-Koninckx C, Mearin ML, Korponay-Szabo IR, Shamir R, Husby S, Ventura A, Branski D, Catassi C, Koletzko S, Maki M, et al. Coeliac disease diagnosis: ESPGHAN 1990 criteria or need for a change? Results of a questionnaire. J Pediatr Gastroenterol Nutr. 2012;54:15–9.CrossRefPubMed Ribes-Koninckx C, Mearin ML, Korponay-Szabo IR, Shamir R, Husby S, Ventura A, Branski D, Catassi C, Koletzko S, Maki M, et al. Coeliac disease diagnosis: ESPGHAN 1990 criteria or need for a change? Results of a questionnaire. J Pediatr Gastroenterol Nutr. 2012;54:15–9.CrossRefPubMed
16.
go back to reference Cummins AG, Roberts-Thomson IC. Prevalence of celiac disease in the Asia-Pacific region. J Gastroenterol Hepatol. 2009;24:1347–51.CrossRefPubMed Cummins AG, Roberts-Thomson IC. Prevalence of celiac disease in the Asia-Pacific region. J Gastroenterol Hepatol. 2009;24:1347–51.CrossRefPubMed
17.
go back to reference Challar MH, Jouma M, Sitzmann FC, Seferian V, Shahin E. Prevalence of asymptomatic celiac disease in a Syrian population sample. JABMS. 2004;6:155–160E. Challar MH, Jouma M, Sitzmann FC, Seferian V, Shahin E. Prevalence of asymptomatic celiac disease in a Syrian population sample. JABMS. 2004;6:155–160E.
18.
go back to reference Marsh MN. Gluten, major histocompatibility complex, and the small intestine. A molecular and immunobiologic approach to the spectrum of gluten sensitivity (‘celiac sprue’). Gastroenterology. 1992;102:330–54.CrossRefPubMed Marsh MN. Gluten, major histocompatibility complex, and the small intestine. A molecular and immunobiologic approach to the spectrum of gluten sensitivity (‘celiac sprue’). Gastroenterology. 1992;102:330–54.CrossRefPubMed
19.
20.
go back to reference Bunce M, O'Neill CM, Barnardo MC, Krausa P, Browning MJ, Morris PJ, Welsh KI. Phototyping: comprehensive DNA typing for HLA-A, B, C, DRB1, DRB3, DRB4, DRB5 & DQB1 by PCR with 144 primer mixes utilizing sequence-specific primers (PCR-SSP). Tissue Antigens. 1995;46:355–67.CrossRefPubMed Bunce M, O'Neill CM, Barnardo MC, Krausa P, Browning MJ, Morris PJ, Welsh KI. Phototyping: comprehensive DNA typing for HLA-A, B, C, DRB1, DRB3, DRB4, DRB5 & DQB1 by PCR with 144 primer mixes utilizing sequence-specific primers (PCR-SSP). Tissue Antigens. 1995;46:355–67.CrossRefPubMed
21.
go back to reference Scola L, Lio D, Candore G, Forte GI, Crivello A, Colonna-Romano G, Pes MG, Carru C, Ferrucci L, Deiana L, et al. Analysis of HLA-DRB1, DQA1, DQB1 haplotypes in Sardinian centenarians. Exp Gerontol. 2008;43:114–8.CrossRefPubMed Scola L, Lio D, Candore G, Forte GI, Crivello A, Colonna-Romano G, Pes MG, Carru C, Ferrucci L, Deiana L, et al. Analysis of HLA-DRB1, DQA1, DQB1 haplotypes in Sardinian centenarians. Exp Gerontol. 2008;43:114–8.CrossRefPubMed
22.
go back to reference Megiorni F, Mora B, Bonamico M, Barbato M, Nenna R, Maiella G, Lulli P, Mazzilli MC. HLA-DQ and risk gradient for celiac disease. Hum Immunol. 2009;70:55–9.CrossRefPubMed Megiorni F, Mora B, Bonamico M, Barbato M, Nenna R, Maiella G, Lulli P, Mazzilli MC. HLA-DQ and risk gradient for celiac disease. Hum Immunol. 2009;70:55–9.CrossRefPubMed
23.
go back to reference Leonard MM, Sapone A, Catassi C, Fasano A. Celiac disease and nonceliac gluten sensitivity: a review. JAMA. 2017;318:647–56.CrossRefPubMed Leonard MM, Sapone A, Catassi C, Fasano A. Celiac disease and nonceliac gluten sensitivity: a review. JAMA. 2017;318:647–56.CrossRefPubMed
24.
go back to reference Lionetti E, Gatti S, Pulvirenti A, Catassi C. Celiac disease from a global perspective. Best Pract Res Clin Gastroenterol. 2015;29:365–79.CrossRefPubMed Lionetti E, Gatti S, Pulvirenti A, Catassi C. Celiac disease from a global perspective. Best Pract Res Clin Gastroenterol. 2015;29:365–79.CrossRefPubMed
25.
go back to reference Megiorni F, Pizzuti A. HLA-DQA1 and HLA-DQB1 in celiac disease predisposition: practical implications of the HLA molecular typing. J Biomed Sci. 2012;19:88.CrossRefPubMedPubMedCentral Megiorni F, Pizzuti A. HLA-DQA1 and HLA-DQB1 in celiac disease predisposition: practical implications of the HLA molecular typing. J Biomed Sci. 2012;19:88.CrossRefPubMedPubMedCentral
26.
go back to reference Malamut G, Cellier C. Complications of coeliac disease. Best Pract Res Clin Gastroenterol. 2015;29:451–8.CrossRefPubMed Malamut G, Cellier C. Complications of coeliac disease. Best Pract Res Clin Gastroenterol. 2015;29:451–8.CrossRefPubMed
27.
go back to reference Mohammed MA, Omar NM, Shebl AM, Mansour AH, Elmasry E, Othman G. Celiac disease prevalence and its HLA-genotypic profile in Egyptian patients with type 1 diabetes mellitus. Trends in Medical Research. 2014;9:81–97.CrossRef Mohammed MA, Omar NM, Shebl AM, Mansour AH, Elmasry E, Othman G. Celiac disease prevalence and its HLA-genotypic profile in Egyptian patients with type 1 diabetes mellitus. Trends in Medical Research. 2014;9:81–97.CrossRef
28.
go back to reference Ayesh BM, Zaqout EK, Yassin MM. HLA-DQ2 and -DQ8 haplotypes frequency and diagnostic utility in celiac disease patients of Gaza strip, Palestine. Auto Immun Highlights. 2017;8:11.CrossRefPubMedPubMedCentral Ayesh BM, Zaqout EK, Yassin MM. HLA-DQ2 and -DQ8 haplotypes frequency and diagnostic utility in celiac disease patients of Gaza strip, Palestine. Auto Immun Highlights. 2017;8:11.CrossRefPubMedPubMedCentral
29.
go back to reference El-Akawi ZJ, Al-Hattab DM, Migdady MA. Frequency of HLA-DQA1*0501 and DQB1*0201 alleles in patients with coeliac disease, their first-degree relatives and controls in Jordan. Ann Trop Paediatr. 2010;30:305–9.CrossRefPubMed El-Akawi ZJ, Al-Hattab DM, Migdady MA. Frequency of HLA-DQA1*0501 and DQB1*0201 alleles in patients with coeliac disease, their first-degree relatives and controls in Jordan. Ann Trop Paediatr. 2010;30:305–9.CrossRefPubMed
30.
go back to reference Piancatelli D, Ben El Barhdadi I, Oumhani K, Sebastiani P, Colanardi A, Essaid A. HLA typing and celiac disease in Moroccans. Med Sci (Basel). 2017;5:1–11. Piancatelli D, Ben El Barhdadi I, Oumhani K, Sebastiani P, Colanardi A, Essaid A. HLA typing and celiac disease in Moroccans. Med Sci (Basel). 2017;5:1–11.
31.
go back to reference Margaritte-Jeannin P, Babron MC, Bourgey M, Louka AS, Clot F, Percopo S, Coto I, Hugot JP, Ascher H, Sollid LM, et al. HLA-DQ relative risks for coeliac disease in European populations: a study of the European genetics cluster on coeliac disease. Tissue Antigens. 2004;63:562–7.CrossRefPubMed Margaritte-Jeannin P, Babron MC, Bourgey M, Louka AS, Clot F, Percopo S, Coto I, Hugot JP, Ascher H, Sollid LM, et al. HLA-DQ relative risks for coeliac disease in European populations: a study of the European genetics cluster on coeliac disease. Tissue Antigens. 2004;63:562–7.CrossRefPubMed
32.
go back to reference Liu E, Lee HS, Aronsson CA, Hagopian WA, Koletzko S, Rewers MJ, Eisenbarth GS, Bingley PJ, Bonifacio E, Simell V, et al. Risk of pediatric celiac disease according to HLA haplotype and country. N Engl J Med. 2014;371:42–9.CrossRefPubMedPubMedCentral Liu E, Lee HS, Aronsson CA, Hagopian WA, Koletzko S, Rewers MJ, Eisenbarth GS, Bingley PJ, Bonifacio E, Simell V, et al. Risk of pediatric celiac disease according to HLA haplotype and country. N Engl J Med. 2014;371:42–9.CrossRefPubMedPubMedCentral
33.
go back to reference Stankovic B, Radlovic N, Lekovic Z, Ristic D, Radlovic V, Nikcevic G, Kotur N, Vucicevic K, Kostic T, Pavlovic S, Zukic B. HLA genotyping in pediatric celiac disease patients. Bosn J Basic Med Sci. 2014;14:171–6.CrossRefPubMedPubMedCentral Stankovic B, Radlovic N, Lekovic Z, Ristic D, Radlovic V, Nikcevic G, Kotur N, Vucicevic K, Kostic T, Pavlovic S, Zukic B. HLA genotyping in pediatric celiac disease patients. Bosn J Basic Med Sci. 2014;14:171–6.CrossRefPubMedPubMedCentral
34.
go back to reference Zamani M, Modares-Sadegi M, Shirvani F, Zamani H, Emami MH. The involvement of the HLA-DQB1 alleles in the risk and the severity of Iranian coeliac disease patients. Int J Immunogenet. 2014;41:312–7.CrossRefPubMed Zamani M, Modares-Sadegi M, Shirvani F, Zamani H, Emami MH. The involvement of the HLA-DQB1 alleles in the risk and the severity of Iranian coeliac disease patients. Int J Immunogenet. 2014;41:312–7.CrossRefPubMed
35.
go back to reference Murray JA, Moore SB, Van Dyke CT, Lahr BD, Dierkhising RA, Zinsmeister AR, Melton LJ 3rd, Kroning CM, El-Yousseff M, Czaja AJ. HLA DQ gene dosage and risk and severity of celiac disease. Clin Gastroenterol Hepatol. 2007;5:1406–12.CrossRefPubMedPubMedCentral Murray JA, Moore SB, Van Dyke CT, Lahr BD, Dierkhising RA, Zinsmeister AR, Melton LJ 3rd, Kroning CM, El-Yousseff M, Czaja AJ. HLA DQ gene dosage and risk and severity of celiac disease. Clin Gastroenterol Hepatol. 2007;5:1406–12.CrossRefPubMedPubMedCentral
36.
go back to reference Hernandez-Charro B, Donat E, Miner I, Aranburu E, Sanchez-Valverde F, Ramos-Arroyo MA. Modifying effect of HLA haplotypes located trans to DQB1*02-DRB1*03 in celiac patients of southern Europe. Tissue Antigens. 2008;71:213–8.CrossRefPubMed Hernandez-Charro B, Donat E, Miner I, Aranburu E, Sanchez-Valverde F, Ramos-Arroyo MA. Modifying effect of HLA haplotypes located trans to DQB1*02-DRB1*03 in celiac patients of southern Europe. Tissue Antigens. 2008;71:213–8.CrossRefPubMed
Metadata
Title
HLA-DQ2 and -DQ8 genotype frequency in Syrian celiac disease children: HLA-DQ relative risks evaluation
Authors
Hossam Murad
Batoul Jazairi
Issam Khansaa
Doaa Olabi
Lina Khouri
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Gastroenterology / Issue 1/2018
Electronic ISSN: 1471-230X
DOI
https://doi.org/10.1186/s12876-018-0802-2

Other articles of this Issue 1/2018

BMC Gastroenterology 1/2018 Go to the issue