Interleukin-10 haplotypes in Celiac Disease in the Spanish population.
BACKGROUND
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. The IL-10 gene 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 the IL-10 promoter 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.


CONCLUSIONS
The IL-10 polymorphisms 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.
Department of Clinical Immunology, Hospital Clínico San Carlos, Madrid, Spain. connunez@usc.es
Concepción
C
Núñez
Diana
D
Alecsandru
Jezabel
J
Varadé
Isabel
I
Polanco
Carlos
C
Maluenda
Miguel
M
Fernández-Arquero
Emilio G
EG
de la Concha
Elena
E
Urcelay
Alfonso
A
Martínez
D016022:Case-Control Studies; D002446:Celiac Disease / Q000235:genetics*; D005260:Female; D006580:Genetic Carrier Screening; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D018895:Microsatellite Repeats; D020641:Polymorphism, Single Nucleotide; D013030:Spain
D016753:Interleukin-10