Proceedings of the 10th International Colloquium on Paratuberculosis

#177
Associations between CARD15 polymorphisms, MAP DNA in blood and lactase persistence in
a Crohn’s disease case-control study in North-Spain
Ramon A Juste, Natalia Elguezabal, Susana Chamorro, Elena Molina, Joseba M Garrido, Sabino Riestra, Ruth
de Francisco, Luis Rodrigo
NEIKER-Tecnalia, Spain; Hospital Universitario Central de Asturias, Spain
Polymorphisms in CARD15 gene have been associated with Crohn’s disease (CD). Also an epidemiologic
association between national CD incidence and lactase persistence frequencies has been reported. CARD15
polymorphisms and presence <strong>of</strong> MAP DNA in blood results are controversial. Here we test <strong>the</strong> association <strong>of</strong>
R702W, G908R and L1007fs polymorphisms in CARD15, as well as CT-13910 polymorphism in <strong>the</strong> lactase
gene with <strong>the</strong> presence <strong>of</strong> Mycobacterium avium subsp. paratuberculosis (MAP) DNA in blood and <strong>the</strong> diagnosis
<strong>of</strong> CD.
Blood samples from 150 CD patients and 65 blood donors from Asturias (Spain) were genotyped by
RTi-PCR for CARD15 and by PCR and restriction enzyme digestion for lactase. MAP was detected by nested
PCR. A marginally significant association between CD and MAP in blood was found (controls: 37.7%, CD:
25.6%, p=0.0598). NOD2 R709W variant was associated with higher rate <strong>of</strong> MAP detection in blood (60.0%
versus 27.8%, p=0.0048). Associations between CD and genotypes were weak, but were partially confirmed by
comparing allelic frequencies. The T allele in lactase gene was more frequent in CD patients (61.9%) than in
controls (47.1%)(p=0.0275), while only marginal differences were observed for CARD15 at R709W (5.0% vs.
6.4%, p=0.3641) and L1007fs (3.9% vs. 0.8%, p=0.0792). Logistic regression analysis yielded odds ratios <strong>of</strong>
over 4 between both genes and MAP in blood.
These results confirm an association <strong>of</strong> genetic factors to CD and to MAP infection in humans. The observation
<strong>of</strong> higher frequencies <strong>of</strong> MAP in controls than in patients is controversial, but has been explained as
<strong>the</strong> result <strong>of</strong> bacterial reduction by <strong>the</strong> antibiotic effect <strong>of</strong> standard CD <strong>the</strong>rapy. Alternatively, it could represent
evidence <strong>of</strong> a more continuous and efficient boosting <strong>of</strong> protective immune mechanisms in slow infections. This
hypo<strong>the</strong>sis matches better with observation <strong>of</strong> more frequent MAP-haemia in herds without paratuberculosis
clinical cases and in vaccinated animals.
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