The interferon gamma gene in celiac disease: augmented expression correlates with tissue damage but no evidence for genetic susceptibility.
Celiac disease (CD) is a complex genetic disorder characterized by gluten intolerance. The Th1 immune response, with a key position for interferon gamma (IFN-gamma), is an important determinant of intestinal remodeling in CD. We aimed at further ascertaining the role of IFN-gamma, either as a genetic factor in the etiology, or as a facilitator of disease initiation/progression. Duodenal biopsies were sampled across distinct histopathological stages of the disease, including refractory CD (RCD), and used to determine IFN-gamma gene (IFNG) expression by real-time RT-PCR. INFG expression correlated with the extent of tissue restructuring, reaching a 240-fold higher expression in total villous atrophy compared to healthy tissue. CD and RCD patients with similar lesions had comparable expression levels. Interestingly, patients in complete remission still had 7.6-fold residual over-expression. An INFG marker was tested in three cohorts of Dutch patients for both genetic linkage and association. Linkage analysis yielded no significant scores for IFNG or its flanking markers. In addition, IFNG allele frequencies were not differently distributed between cases and controls. Likewise, all alleles were randomly transmitted to affected children in parents-case trios. There is no evidence for IFNG as a predisposing gene in CD, despite its enhanced expression in patients in complete remission.
Department of Biomedical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands. m.c.wapenaar@med.uu.nl
Martin C
MC
Wapenaar
Martine J
MJ
van Belzen
Justin H
JH
Fransen
Aranzazu Fariña
AF
Sarasqueta
Roderick H J
RH
Houwen
Jos W R
JW
Meijer
Chris J J
CJ
Mulder
Cisca
C
Wijmenga
D000328:Adult; D001284:Atrophy; D002446:Celiac Disease / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D018450:Disease Progression; D004386:Duodenum / Q000737:chemistry / Q000473:pathology; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D040582:Inheritance Patterns; D007371:Interferon-gamma / Q000235:genetics* / Q000502:physiology; D008297:Male; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D015854:Up-Regulation
D007371:Interferon-gamma