Coeliac disease is an autoimmune disorder with genetic predisposition. The aim was to determine the frequency of HLA-DQ2 and HLA-DQ8 in Czech and Slovak patients and the healthy population. The study included 127 patients and 66 healthy volunteers. HLA-DQ2 was identified in 85.03% patients, and 24.24% healthy individuals (P=0.0001; OR17.7632; CI=8.4347-37.4088). HLA-DQ8 was identified in 11.81% patients and 15.5% healthy individuals. HLA-DQ8 occurred more often in HLA-DQ2-negative patients compared to HLA-DQ2-positive patients (P=0.0494; OR3.5; CI 1.0428-11.7468). At least one of the studied HLA-variants was found more often in patients than in healthy individuals (P=0.0001; OR58.8; CI 7.6856-449.8602).

• MeSH
• celiakie genetika   patologie   MeSH
• etnicita genetika   MeSH
• frekvence genu MeSH
• genetická predispozice k nemoci MeSH
• genetické asociační studie MeSH
• haplotypy genetika   MeSH
• HLA-DQ antigeny genetika   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Slovenská republika MeSH
• Názvy látek
• HLA-DQ antigeny MeSH
• HLA-DQ2 antigen MeSH Prohlížeč
• HLA-DQ8 antigen MeSH Prohlížeč

BACKGROUND: Approximately 10-28 % of patients experience adverse drug reactions related to treatment with thiopurines. The most serious reaction is myelosuppression, typically manifested as leucopenia, which occurs in approximately 2-5 % of patients. Other adverse drug reactions that often accompany thiopurine therapy are pancreatitis, hepatotoxicity, allergic reactions, digestive intolerance, arthralgia, febrile conditions, and rash. OBJECTIVE: The objective of this study was to assess the relationship between variant alleles of thiopurine S-methyltransferase (SNPs 238G > C, 460G > A and 719A > G), inosine triphosphate diphosphatase (SNPs 94C > A and IVS2 + 21A > C), and xanthine dehydrogenase (837C > T) and the occurrence of adverse drug reactions to azathioprine therapy. METHODS: Genotype was determined for 188 Caucasians diagnosed with inflammatory bowel disease treated with a standard dose of azathioprine (1.4-2.0 mg/kg/day). Allelic variants were determined by PCR-REA and real-time PCR methods. Results were statistically evaluated by use of Fisher's test and by odds ratio calculation. RESULTS: Variant genotype thiopurine S-methyltransferase predisposes to development of leucopenia (P = 0.003, OR = 5, CI 95 %, 1.8058-13.8444). Although not statistically significant, we observed a trend that suggested correlation between the occurrence of digestive intolerance and the variant genotype inosine triphosphate diphosphatase (P = 0.1102; OR 15.63, CI 95 %, 1.162-210.1094), and between the occurrence of pancreatitis and the variant allele xanthine dehydrogenase 837T (P = 0.1124; OR 12,1, CI 95 %, 1.15-126.37). CONCLUSION: The variant genotype thiopurine S-methyltransferase has been associated with the occurrence of leucopenia. The involvement of polymorphisms in inosine triphosphate diphosphatase and xanthine dehydrogenase genes in the development of digestive intolerance and pancreatitis will require further verification.

• MeSH
• azathioprin škodlivé účinky   terapeutické užití   MeSH
• gastrointestinální nemoci chemicky indukované   genetika   MeSH
• genetická predispozice k nemoci MeSH
• genotyp MeSH
• idiopatické střevní záněty farmakoterapie   MeSH
• imunosupresiva škodlivé účinky   terapeutické užití   MeSH
• leukopenie chemicky indukované   genetika   MeSH
• lidé MeSH
• methyltransferasy genetika   metabolismus   MeSH
• pankreatitida chemicky indukované   genetika   MeSH
• polymerázová řetězová reakce metody   MeSH
• polymorfismus genetický * MeSH
• prohibitiny MeSH
• regulace genové exprese MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• azathioprin MeSH
• imunosupresiva MeSH
• methyltransferasy MeSH
• PHB2 protein, human MeSH Prohlížeč
• prohibitiny MeSH
• thiopurine methyltransferase MeSH Prohlížeč