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

Aslı Eldem; Tülay Kılıçaslan Ayna; Maşallah Baran; Mustafa Soyöz; İbrahim Pirim

doi:10.1055/s-0041-1722856

Journal of Pediatric Genetics, Table of Contents

J Pediatr Genet 2022; 11(03): 192-197
DOI: 10.1055/s-0041-1722856

Original Article

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

Aslı Eldem

¹Department of Medical Biology and Genetics, Izmir Katip Celebi University, Izmir Tepecik Education and Research Hospital Tissue Typing Laboratory, İzmir, Turkey

,

Tülay Kılıçaslan Ayna

¹Department of Medical Biology and Genetics, Izmir Katip Celebi University, Izmir Tepecik Education and Research Hospital Tissue Typing Laboratory, İzmir, Turkey

,

Maşallah Baran

²Department of Pediatric Gastroenterology, Izmir Katip Celebi University, Izmir Tepecik Education and Research Hospital, İzmir, Turkey

,

Mustafa Soyöz

¹Department of Medical Biology and Genetics, Izmir Katip Celebi University, Izmir Tepecik Education and Research Hospital Tissue Typing Laboratory, İzmir, Turkey

,

İbrahim Pirim

¹Department of Medical Biology and Genetics, Izmir Katip Celebi University, Izmir Tepecik Education and Research Hospital Tissue Typing Laboratory, İzmir, Turkey

› Author Affiliations

Abstract

Celiac 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.

Keywords

celiac disease - human leukocyte antigen-DQ polymorphism - IL-17 polymorphism - gluten - pediatric

Full Text

References

References
1 Sollid LM. Coeliac disease: dissecting a complex inflammatory disorder. Nat Rev Immunol 2002; 2 (09) 647-655
2 Shiina T, Hosomichi K, Inoko H, Kulski JK. The HLA genomic loci map: expression, interaction, diversity and disease. J Hum Genet 2009; 54 (01) 15-39
3 Goodwin G. Type 1 diabetes mellitus and celiac disease: distinct autoimmune disorders that share common pathogenic mechanisms. Horm Res Paediatr 2019; 92 (05) 285-292
4 Faghih M, Barbartabar Z, Nasiri Z, Nejad RM. The role of Th1 and Th17 in the pathogenesis of celiac disease. Gastroenterol Hepatol Open Access 2018; 9 (02) 83-87
5 Castellanos-Rubio A, Santin I, Irastorza I, Castaño L, Carlos Vitoria J, Ramon Bilbao J. Castellanos-RA. TH17 (and TH1) signatures of intestinal biopsies of CD patients in response to gliadin. Autoimmunity 2009; 42 (01) 69-73
6 Murakami M, Okuyama Y, Ogura H. et al. Local microbleeding facilitates IL-6- and IL-17-dependent arthritis in the absence of tissue antigen recognition by activated T cells. J Exp Med 2011; 208 (01) 103-114
7 Tesmer LA, Lundy SK, Sarkar S, Fox DA. Th17 cells in human disease. Immunol Rev 2008; 223: 87-113
8 Monteleone I, Sarra M, Del Vecchio Blanco G. et al. Characterization of IL-17A-producing cells in celiac disease mucosa. J Immunol 2010; 184 (04) 2211-2218
9 Lahdenperä AI, Hölttä V, Ruohtula T. et al. Up-regulation of small intestinal interleukin-17 immunity in untreated coeliac disease but not in potential coeliac disease or in type 1 diabetes. Clin Exp Immunol 2012; 167 (02) 226-234
10 Husby S, Koletzko S, Korponay-Szabó IR. et al; ESPGHAN Working Group on Coeliac Disease Diagnosis, ESPGHAN Gastroenterology Committee, European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr 2012; 54 (01) 136-160
11 Yang LJ, Gao W, Bai JY. et al. Correlation between interleukin-17 gene polymorphism and gastric cancer susceptibility in Han Chinese population. Eur Rev Med Pharmacol Sci 2016; 20 (07) 1271-1282
12 Akbulut UE, Çebi AH, Sağ E, İkbal M, Çakır M. Interleukin-6 and interleukin-17 gene polymorphism association with celiac disease in children. Turk J Gastroenterol 2017; 28 (06) 471-475
13 Khan D, Ansar Ahmed S. Regulation of IL-17 in autoimmune diseases by transcriptional factors and microRNAs. Front Genet 2015; 6: 236
14 Lahdenperä AI, Fälth-Magnusson K, Högberg L, Ludvigsson J, Vaarala O. Expression pattern of T-helper 17 cell signaling pathway and mucosal inflammation in celiac disease. Scand J Gastroenterol 2014; 49 (02) 145-156
15 van Leeuwen MA, Lindenbergh-Kortleve DJ, Raatgeep HC. et al. Increased production of interleukin-21, but not interleukin-17A, in the small intestine characterizes pediatric celiac disease. Mucosal Immunol 2013; 6 (06) 1202-1213
16 Wang JY, Shyur SD, Wang WH. et al. The polymorphisms of interleukin 17A (IL17A) gene and its association with pediatric asthma in Taiwanese population. Allergy 2009; 64 (07) 1056-1060
17 Holster A, Teräsjärvi J, Lauhkonen E. et al. IL-17A gene polymorphism rs2275913 is associated with the development of asthma after bronchiolitis in infancy. Allergol Int 2018; 67 (01) 109-113
18 Maalmi H, Beraies A, Charad R, Ammar J, Hamzaoui K, Hamzaoui A. IL-17A and IL-17F genes variants and susceptibility to childhood asthma in Tunisia. J Asthma 2014; 51 (04) 348-354
19 Baştürk A, Artan R, Yilmaz A. The incidence of HLA-DQ2/DQ8 in Turkish children with celiac disease and a comparison of the geographical distribution of HLA-DQ. Prz Gastroenterol 2017; 12 (04) 256-261
20 Tüysüz B, Dursun A, Kutlu T. et al. HLA-DQ alleles in patients with celiac disease in Turkey. Tissue Antigens 2001; 57 (06) 540-542
21 Fallah H, Akbari MT, Mirzajani S. et al. Association between HLA alleles and risk of celiac disease in Iranian patients. Hum Antibodies 2020; 28 (02) 123-129
22 Krini M, Chouliaras G, Kanariou M. et al. HLA class II high-resolution genotyping in Greek children with celiac disease and impact on disease susceptibility. Pediatr Res 2012; 72 (06) 625-630
23 Vidan-Jeras B. When type 1 diabetes meets celiac disease. HLA 2018; 92 (Suppl. 02) 64-66
24 Noble JA, Valdes AM. Genetics of the HLA region in the prediction of type 1 diabetes. Curr Diab Rep 2011; 11 (06) 533-542
25 Petrone A, Battelino T, Krzisnik C. et al. Similar incidence of type 1 diabetes in two ethnically different populations (Italy and Slovenia) is sustained by similar HLA susceptible/protective haplotype frequencies. Tissue Antigens 2002; 60 (03) 244-253
26 Hagopian W, Lee HS, Liu E. et al; TEDDY Study Group. Co-occurrence of Type 1 diabetes and celiac disease autoimmunity. Pediatrics 2017; 140 (05) e20171305
27 Nguyen C, Varney MD, Harrison LC, Morahan G. Definition of high-risk type 1 diabetes HLA-DR and HLA-DQ types using only three single nucleotide polymorphisms. Diabetes 2013; 62 (06) 2135-2140
28 Jores RD, Frau F, Cucca F. et al. HLA-DQB1*0201 homozygosis predisposes to severe intestinal damage in celiac disease. Scand J Gastroenterol 2007; 42 (01) 48-53
29 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 (04) 305-309
30 LIorente-Alonso MJ, Fernandez-Acenero MJ, Sebastian M. Gluten intolerance: sex and age-related features. Can J Gastroenterol 2006; 20: 719-722