Elçin Latife KURTOĞLU, İbrahim TEKEDERELİ

Çölyak Hastalığı Ön Tanısı Almış Bireylerde HLA-DQ2 ve HLA-DQ8 Genotip Sıklıkları

Amaç: Çölyak hastalığı yaygın, ailesel, otoimmün bir gastrointestinal hastalıktır. Bu durum, buğday, çavdar ve arpada bulunan diyetteki protein glutene karşı hassasiyetten kaynaklanır. Çölyak hastalığı insan lökosit antijenleriyle (HLA) güçlü bir genetik ilişkiye sahiptir. Çölyak hastalığı için birincil duyarlılık genotipi HLA-DQA1*05 ve DQB1*02'den oluşan HLA-DQ2'dir, vakaların geri kalan kısmı HLA-DQA1*03 ve DQB1*03:02'den oluşan HLA-DQ8 ile ilişkilidir. Bu çalışmanın amacı, Malatya ilinde çölyak ön tanısı almış çocuk hastalarda DQ2 ve DQ8 genotiplerinin sıklığını araştırmaktır. Gereç ve Yöntem: 578 bireyden (338 kadın/240 erkek) DNA örnekleri HLA-DQA1 ve DQB1 için SSP-PCR yöntemine göre genotiplenmiştir. Bulgular: 578 olgunun 304'ünde (% 52.59) HLA-DQ2, 86'sında (% 14.87) HLA-DQ8, 28'inde (% 4.84) HLA-DQ2 /DQ8 tespit edilmiştir ve 160 hastanın ise (% 27.68) DQ2 veya DQ8 genotiplerinden herhangi birine sahip olmadığı görülmüştür. En sık rastlanan alleller DQA1*05 (% 76.64) ve DQB1*02 (% 61.41) olarak belirlenmiştir. Sonuç: Sonuç olarak; çalışmamızdaki DQ2/DQ8 genotiplerinin sıklıklarının, literatür ile benzer olduğu tespit edilmiştir.

Anahtar Kelimeler:

HLA-DQ2, HLA-DQ8, Çölyak Hastalığı

Frequencies of HLA-DQ2/DQ8 Genotypes in Patients Prediagnosed as Celiac Disease

Aim: Celiac disease is a common, familial, autoimmune gastrointestinal disease. It is caused by sensitivity to the dietary protein gluten, which is present in wheat, rye, and barley. Celiac disease has a strong genetic association with human leukocyte antigens (HLA). The primary susceptibility allele for Celiac disease is HLA-DQ2 which is composed of HLA-DQA1*05 and DQB1*02, rest of the cases is related to HLA-DQ8 that is composed of HLA-DQA1*03 DQB1*03:02. The aim of the present study was to investigate the prevalence of the DQ2 and DQ8 genotypes in children with prediagnosed as celiac disease in city of Malatya, Turkey. Materials and Methods: DNA samples from 578 individuals (338 female, 240 male) were genotyped for HLA DQA1 and DQB1 based on SSP-PCR method. Results: Among the 578 cases, 304 (52.59%) had the genotype HLA-DQ2 and 86 (14.87 %) had HLA-DQ8, 28 (4.84 %) had HLA-DQ2/DQ8, and 160 (27.6 8%) did not have any of these genotypes. The most common alleles in children genotyped for in Malatya were DQA1*05 (76.64 %) and DQB1*02 (61.41 %). Conclusion: In conclusion, the frequencies of the DQ2/DQ8 genotypes in our study are similar to those reported in Turkey, previously.

Keywords:

HLA-DQ2, HLA-DQ8, Celiac Disease,

PDF

___

1. Vidales MC, Zubillaga P, Zubillaga I, Alfonso-Sanchez MA. Allele and haplotype frequencies for HLA class II (DQA1 and DQB1) loci in patients with celiac disease from Spain. Hum immunol 2004;65(4):352-8.
2. Wu J, Xia B, von Blomberg BM, Zhao C, Yang XW, Crusius JB, et al. Coeliac disease in China, a field waiting for exploration. Rev Esp Enferm Dig 2010;102(8):472-7.
3. Kuloglu Z, Doganci T, Kansu A, Demirceken F, Duman M, Tutkak H, et al. HLA types in Turkish children with celiac disease. Turk J Pediatr 2008;50(6):515-20.
4. Neuhausen SL, Weizman Z, Camp NJ, Elbedour K, Sheffield VC, Zone JJ, et al. HLA DQA1-DQB1 genotypes in Bedouin families with celiac disease. Hum immunol 2002;63(6):502-7.
5. Walkowiak J, Blask-Osipa A, Lisowska A, Oralewska B, Pogorzelski A, Cichy W, et al. Cystic fibrosis is a risk factor for celiac disease. Acta Biochim Pol 2010;57(1):115-8.
6. Tjon JM, van Bergen J, Koning F. Celiac disease: how complicated can it get? Immunogenet 2010;62(10):641-51.
7. Clot F, Babron MC. Genetics of celiac disease. Mol Genet Metab 2000;71(1-2):76-80.
8. Costantini S, Rossi M, Colonna G, Facchiano AM. Modelling of HLA-DQ2 and its interaction with gluten peptides to explain molecular recognition in celiac disease. J Mol Graph Model 2005;23(5):419-31.
9. Alarida K, Harown J, Di Pierro MR, Drago S, Catassi C. HLA-DQ2 and -DQ8 genotypes in celiac and healthy Libyan children. Dig Liver Dis 2010;42(6):425-7.
10. Tuysuz B, Dursun A, Kutlu T, Sokucu S, Cine N, Suoglu O, et al. HLA-DQ alleles in patients with celiac disease in Turkey. Tissue antigens 2001;57(6):540-2.
11. Megiorni F, Mora B, Bonamico M, Barbato M, Nenna R, Maiella G, et al. HLA-DQ and risk gradient for celiac disease. Hum immunol 2009;70(1):55-9.
12. Tollefsen S, Arentz-Hansen H, Fleckenstein B, Molberg O, Raki M, Kwok WW, et al. HLA-DQ2 and -DQ8 signatures of gluten T cell epitopes in celiac disease. J Clin Invest 2006;116(8):2226-36.
13. 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.
14. Ceylan G, Tekedereli İ. Çölyak Hastalığı Olan Bir Ailede HLA Tiplendirmesi. Gazi Tıp Derg 2009;20(4):181-3.
15. Piccini B, Vascotto M, Serracca L, Luddi A, Margollicci MA, Balestri P, et al. HLA-DQ typing in the diagnostic algorithm of celiac disease. Rev Esp Enferm Dig 2012;104(5):248-54.
16. Castro-Antunes MM, Crovella S, Brandao LA, Guimaraes RL, Motta ME, Silva GA. Frequency distribution of HLA DQ2 and DQ8 in celiac patients and first-degree relatives in Recife, northeastern Brazil. Clinics (Sao Paulo) 2011;66(2):227-31.
17. Karell K, Louka AS, Moodie SJ, Ascher H, Clot F, Greco L, et al. HLA types in celiac disease patients not carrying the DQA1*05-DQB1*02 (DQ2) heterodimer: results from the European Genetics Cluster on Celiac Disease. Hum immunol. 2003;64(4):469-77.
18. Biagi F, Bianchi PI, Vattiato C, Marchese A, Trotta L, Badulli C, et al. Influence of HLA-DQ2 and DQ8 on severity in celiac Disease. J Clin Gastroenterol 2012;46(1):46-50.
19. Tumer L, Altuntas B, Hasanoglu A, Soylemezoglu O, Arinsoy T. Pattern of human leukocyte antigens in Turkish children with celiac disease. Pediatr Int 2000;42(6):678-81.
20. Cintado A, Sorell L, Galvan JA, Martinez L, Castaneda C, Fragoso T, et al. HLA DQA1*0501 and DQB1*02 in Cuban celiac patients. Hum immunol 2006;67(8):639-42.