IL6, IL10 and TGFB1 gene polymorphisms in coeliac disease: differences between DQ2 positive and negative patients.
Predisposition to coeliac disease (CD) might be partially due to an individual pattern of hyper-inflammatory biased immune response. One of these patterns of intense response may be linked to the haplotype carrying HLA-DQ2 alleles and TNF -308A allele. However, 10 % of CD patients do not express the DQ2 heterodimer and these do not usually carry the TNF -308A allele. A similar response might be achieved by genes codifying other cytokines.


OBJECTIVE
To study biallelic polymorphisms in genes codifying for TNFalpha, IL10, IL6 and TGFbeta1 in DQ2 negative CD patients and to compare the results with DQ2 positive patients and healthy controls, in order to establish whether any of these polymorphisms have a role in CD susceptibility.


METHODS
TNF -308 (G > A), IL-6 -174 (G > C) and TGFB1 codon 10 (+ 869, T > C) and codon 25 (+ 915, G > C) polymorphisms and IL-10 haplotype of polymorphisms in positions -1082 (G > A), -819 (C > T) and -592 (C > A) were typed by a SSP-PCR technique.


RESULTS
The distribution of allele frequencies for TNF -308 is different between DQ2 positive CD patients and controls and the same occurs for haplotype frequencies of the IL10 promoter (-1082, -819, -592): The frequencies of the TNF -308A allele (p = 0.027), TNF -308A carriers (p = 0.031) and of IL10GCC haplotype are increased (p = 0.013) in DQ2 positive CD patients. However, the IL6 -174 allele G is more frequent in DQ2 negative patients than in healthy controls (p = 0.018), DQ2 negative controls (p = 0,018), and DQ2 positive patients (p = 0.008).


CONCLUSIONS
DQ2 negative CD patients show an increased frequency of genotypes associated to IL6 high production. These were mainly allele G homozygous for the IL6 gene (-174) polymorphism. The IL6 -174GG genotype (homozygous) may be an additional risk marker for CD in DQ2 negative patients, representing an alternative susceptibility factor for CD when TNF -308A is negative.
Garrote
J A
JA
Unidad de Investigación, Hospital Clínico Universitario, Valladolid, Spain. jgarrote@hcuv.sacyl.es
Arranz
E
E
Gómez-González
E
E
León
A J
AJ
Farré
C
C
Calvo
C
C
Bernardo
D
D
Fernández-Salazar
L
L
Blanco-Quirós
A
A
D000483:Alleles; D002446:Celiac Disease / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D003062:Codon / Q000235:genetics; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006683:HLA-DQ Antigens / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics*; D011110:Polymorphism, Genetic; D013030:Spain / Q000453:epidemiology; D016212:Transforming Growth Factor beta / Q000235:genetics*; D053773:Transforming Growth Factor beta1
D003062:Codon; D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; D015850:Interleukin-6; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D016753:Interleukin-10