Interleukin-10 haplotypes in Celiac Disease in the Spanish population

Concepción Núñez1, Diana Alecsandru1, Jezabel Varadé1, Isabel Polanco2, Carlos Maluenda3, Miguel Fernández‐Arquero1, Emilio G. de la Concha1, Elena Urcelay1, Alfonso Martínez1
1Department of Clinical Immunology, Hospital Clínico San Carlos, Madrid, Spain
2Department of Paediatric Gastroenterology, Hospital La Paz, Madrid, Spain
3Department of Paediatrics, Hospital Clínico San Carlos, Madrid, Spain

Tóm tắt

AbstractBackground

Celiac disease (CD) is a chronic disorder characterized by a pathological inflammatory response after exposure to gluten in genetically susceptible individuals. The HLA complex accounts for less than half of the genetic component of the disease, and additional genes must be implicated. Interleukin-10 (IL-10) is an important regulator of mucosal immunity, and several reports have described alterations of IL-10 levels in celiac patients. TheIL-10gene is located on chromosome 1, and its promoter carries several single nucleotide polymorphisms (SNPs) and microsatellites which have been associated to production levels. Our aim was to study the role of those polymorphisms in susceptibility to CD in our population.

Methods

A case-control and a familial study were performed. Positions -1082, -819 and -592 of theIL-10promoter were typed by TaqMan and allele specific PCR. IL10R and IL10G microsatellites were amplified with labelled primers, and they were subsequently run on an automatic sequencer. In this study 446 patients and 573 controls were included, all of them white Spaniards. Extended haplotypes encompassing microsatellites and SNPs were obtained in families and estimated in controls by the Expectation-Maximization algorithm.

Results

No significant associations after Bonferroni correction were observed in the SNPs or any of the microsatellites. Stratification by HLA-DQ2 (DQA1*0501-DQB1*02) status did not alter the results. When extended haplotypes were analyzed, no differences were apparent either.

Conclusion

TheIL-10polymorphisms studied are not associated with celiac disease. Our data suggest that the IL-10 alteration seen in patients may be more consequence than cause of the disease.

Từ khóa


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