Poly (ADP-ribose) polymerase-1 haplotypes are associated with coeliac disease

In coeliac disease (CD) there is an inflammatory status of the intestinal mucosa because of a high expression of proinflammatory mediators. The nuclear protein poly (ADP-ribose) polymerase-1 (PARP-1) has been implicated in the initial inflammatory response by modulating transcription of inflammation-related genes. The aim of this work was to investigate the role of PARP-1 gene promoter region haplotypes in relation to coeliac disease susceptibility. We analysed a coeliac population consisting of a case-control panel with 120 CD patients and 311 healthy blood donors. A CA microsatellite, as haplotype-defining variant of the whole PARP-1 promoter, was typed using a polymerase chain reaction (PCR) method combined with fluorescence technology. We considered two promoter haplotypes: A defined by short CA alleles (83-87 bp) and B defined by long CA alleles (89-101 bp). Haplotype A was significantly increased within the coeliac patients group (P = 0.007 OR 1.6 95%CI 1.12-2.35). Additionally, we observed a significant dose effect, showing homozygous individuals for haplotype A higher risk for CD susceptibility (P = 0.007, OR 1.79 95%CI 1.14-2.82). Our results provide the first evidence that PARP-1 haplotypes are related with coeliac disease susceptibility.