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Six new coeliac disease loci replicated in an Italian population confirm association with coeliac disease
  1. J Romanos1,
  2. D Barisani2,
  3. G Trynka1,
  4. A Zhernakova3,
  5. M T Bardella4,5,
  6. C Wijmenga1
  1. 1
    Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
  2. 2
    Department of Experimental Medicine, Faculty of Medicine University of Milano-Bicocca, Monza, Italy
  3. 3
    Complex Genetics Section, Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands
  4. 4
    Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan, Italy
  5. 5
    Department of Medical Sciences, University of Milan, Milan, Italy
  1. C Wijmenga, Department of Genetics, University Medical Center Groningen, PO Box 30001, 9700 RB Groningen, The Netherlands; c.wijmenga{at}umcutrecht.nl

Abstract

Background and aims: The first genome wide association study on coeliac disease (CD) and its follow-up have identified eight new loci that contribute significantly towards CD risk. Seven of these loci contain genes controlling adaptive immune responses, including IL2/IL21 (4q27), RGS1 (1q31), IL18RAP (2q11–2q12), CCR3 (3p21), IL12A (3q25–3q26), TAGAP (6q25) and SH2B3 (12q24).

Methods: We selected the nine most associated single nucleotide polymorphisms to tag the eight new loci in an Italian cohort comprising 538 CD patients and 593 healthy controls.

Results: Common variation in IL2/IL21, RGS1, IL12A/SCHIP and SH2B3 was associated with susceptibility to CD in our Italian cohort. The LPP and TAGAP regions also showed moderate association, whereas there was no association with CCR3 and IL18RAP.

Conclusion: This is the first replication study of six of the eight new CD loci; it is also the first CD association study in a southern European cohort. Our results may imply there is a genuine population difference across Europe regarding the loci contributing to CD.

http://dx.doi.org/10.1136/jmg.2008.061457

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    Footnotes

    • JR and DB contributed equally to this work

    • Funding: The study was supported by grants from the Celiac Disease Consortium (an innovative cluster approved by the Netherlands Genomics Initiative and partly funded by the Dutch Government, grant BSIK03009 to CW) and KP6 EU grant 036383 (PREVENTCD).

    • Competing interests: None.

    • Patient consent: Obtained.