RESUMO
Celiac disease (CD) is a complex and multifactorial disease, defined as a malabsorptive disorder of the small intestine resulting from ingestion of gluten. Genetic susceptibility to CD has been associated with human leukocyte antigen (HLA)-DQ2 heterodimer, encoded by the DQA1*0501 and DQB1*02 genes. However, HLA risk factors do not explain the whole genetic predisposition: not all DQ2-encoding haplotypes confer equal susceptibility to CD. The aim of the present work was to confirm the aforementioned findings in a southern European population. With this purpose, 136 unrelated children diagnosed with CD were typed at the DNA level for HLA-DQA1 and -DQB1 loci. Patients are currently attended at the Donostia Hospital (province of Guipúzcoa, Spain). HLA class II typing was performed by polymerase chain reaction-sequence specific primer procedures. Conspicuous frequencies of the alleles associated with susceptibility to CD were observed (DQA1*0501: 0.592, DQB1*0201: 0.471). Accordingly, the haplotypes DQA1*0501-DQB1*0201 and DQA1*0201-DQB1*0202 revealed a strong linkage disequilibrium (18.84% and 18.75%, respectively) when compared with the Spanish general population. Of the total sample, 93.4% (127 individuals) were carriers of DQ2 heterodimer, either in homozygosis or in heterozygosis. This percentage coincides with figures reported in previous studies, implying the effect of other genes in the development of CD.
Assuntos
Doença Celíaca/genética , Frequência do Gene , Antígenos HLA-DQ/genética , Glicoproteínas de Membrana/genética , Adolescente , Doença Celíaca/diagnóstico , Doença Celíaca/epidemiologia , Criança , Pré-Escolar , Impressões Digitais de DNA , Feminino , Cadeias alfa de HLA-DQ , Cadeias beta de HLA-DQ , Haplótipos , Humanos , Desequilíbrio de Ligação , Masculino , Fenótipo , Reação em Cadeia da Polimerase , Polimorfismo Genético , Espanha/epidemiologiaRESUMO
BACKGROUND: Patients with celiac disease are diagnosed at any age and can exhibit a wide range of clinical manifestations. The reasons for this are unclear. The aim of this study was to investigate a possible correlation between the HLA-DQA1 and HLA-DQB1 genetic markers and clinical features of celiac disease. METHODS: A total of 133 patients with celiac disease were tested for the HLA-DQA1 and HLA-DQB1 genes. Their corresponding allele and haplotype frequency distributions were estimated from the phenotypes found. The results were correlated with data from the clinical records. RESULTS: The DQ2 molecule was found in 93% of the patients, and DQ2 or DQ8 was found in 98%. The DQA1*0201-DQB1*0202 haplotype showed strong linkage disequilibrium. DQ2 homozygosis was significantly associated with female sex, earlier age at diagnosis, and shorter delay between onset of symptoms and diagnosis. Double-dose DQB1*02 (01-02) allele was more frequent in patients with the classic presentation of the disease. CONCLUSIONS: The genetic markers investigated may prove useful for diagnosing and managing celiac disease. With some clinical variables, correlations not previously described were found. These correlations have a moderate strength and, therefore, must be confirmed by other studies.
