Myosin ixb gene region and gluten intolerance: linkage to coeliac disease and a putative dermatitis herpetiformis association

Lotta L.E. Koskinen ¹, Ilma R. Korponay-Szabo ², Keijo Viiri ³, Kati Juuti-Uusitalo ³, Katri Kaukinen ³, Katri Lindfors ³, Kirsi Mustalahti ³, Kalle Kurppa ³, Róza Ádány ⁴, Zsuzsa Pocsai ⁴, György Széles ⁴, Elisabet Einarsdottir ¹, Cisca Wijmenga ⁵, Markku Mäki ³, Jukka Partanen ⁶, Juha Kere ⁷ and Päivi Saavalainen ^1*

¹ University of Helsinki, Finland
² Heim Pal Children’s Hospital, Budapest, and University of Debrecen, Hungary
³ University of Tampere Medical School and Tampere University Hospital, Finland
⁴ University of Debrecen, Hungary
⁵ University Medical Center Utrecht, and University Medical Center Groningen, Netherlands
⁶ Finnish Red Cross Blood Service, Finland
⁷ University of Helsinki, and Karolinska Institutet, Sweden

^* To whom correspondence should be addressed. E-mail: paivi.saavalainen{at}helsinki.fi.

Accepted 4 November 2007

Abstract

Introduction: Coeliac disease is caused by dietary gluten, which triggers chronic inflammation of the small intestine in genetically predisposed individuals. In one-quarter of the patients the disease manifests in the skin as dermatitis herpetiformis. Recently, a novel candidate gene, myosin IXB on chromosome 19p13, was shown to be associated with coeliac disease in the Dutch and Spanish populations. The same gene has previously been associated with inflammatory bowel disease, systemic lupus erythematosus and rheumatoid arthritis risk, making myosin IXB a potential shared risk factor in these inflammatory disorders. Methods: In this study, previously reported myosin IXB variants were tested for genetic linkage and association with coeliac disease in 495 Hungarian and Finnish families and in an additional 270 patients and controls. Results and discussion: The results show significant linkage (LOD 3.76, P=0.00002) to 19p13 which supports the presence of a genuine risk factor for coeliac disease in this locus. Myosin IXB variants were not associated with coeliac disease in this study; however, weak evidence of association with dermatitis herpetiformis was found. The association could not explain the strong linkage seen in both phenotypes, indicating that the role of other neighbouring genes in the region cannot be excluded. Therefore, more detailed genetic and functional studies are required to characterise the role of the myosin IXB gene in both coeliac disease and dermatitis herpetiformis.

Keywords: MYO9B, celiac disease, coeliac disease, dermatitis herpetiformis, myosin IXB

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