BACKGROUND AND AIMS: Development of coeliac disease involves an interaction between environmental factors (especially dietary wheat, rye, and barley antigens) and genetic factors (there is strong inherited disease susceptibility). The known human leucocyte antigen (HLA)-DQ2 and -DQ8 association explains only a minority of disease heritability. A recent study in the Dutch population suggested that genetic variation in the 3' region of myosin IXB (MYO9B) predisposes to coeliac disease. MYO9B is a Rho family GTPase activating protein involved in epithelial cell cytoskeletal organisation. MYO9B is hypothesised to influence intestinal permeability and hence intestinal antigen presentation. METHODS: Four single nucleotide polymorphisms were chosen to tag all common haplotypes of the MYO9B 3' haplotype block (exons 15-27). We genotyped 375 coeliac disease cases and 1366 controls (371 healthy and 995 population based). All individuals were of White UK Caucasian ethnicity. RESULTS: UK healthy control and population control allele frequencies were similar for all MYO9B variants. Case control analysis showed no significant association of any variant or haplotype with coeliac disease. CONCLUSIONS: Genetic variation in MYO9B does not have a major effect on coeliac disease susceptibility in the UK population. Differences between populations, a weaker effect size than originally described, or possibly a type I error in the Dutch study might explain these findings.
BACKGROUND AND AIMS: Development of coeliac disease involves an interaction between environmental factors (especially dietary wheat, rye, and barley antigens) and genetic factors (there is strong inherited disease susceptibility). The known human leucocyte antigen (HLA)-DQ2 and -DQ8 association explains only a minority of disease heritability. A recent study in the Dutch population suggested that genetic variation in the 3' region of myosin IXB (MYO9B) predisposes to coeliac disease. MYO9B is a Rho family GTPase activating protein involved in epithelial cell cytoskeletal organisation. MYO9B is hypothesised to influence intestinal permeability and hence intestinal antigen presentation. METHODS: Four single nucleotide polymorphisms were chosen to tag all common haplotypes of the MYO9B 3' haplotype block (exons 15-27). We genotyped 375 coeliac disease cases and 1366 controls (371 healthy and 995 population based). All individuals were of White UK Caucasian ethnicity. RESULTS: UK healthy control and population control allele frequencies were similar for all MYO9B variants. Case control analysis showed no significant association of any variant or haplotype with coeliac disease. CONCLUSIONS: Genetic variation in MYO9B does not have a major effect on coeliac disease susceptibility in the UK population. Differences between populations, a weaker effect size than originally described, or possibly a type I error in the Dutch study might explain these findings.
Authors: S Bevan; S Popat; C P Braegger; A Busch; D O'Donoghue; K Falth-Magnusson; A Ferguson; A Godkin; L Hogberg; G Holmes; K B Hosie; P D Howdle; H Jenkins; D Jewell; S Johnston; N P Kennedy; G Kerr; P Kumar; R F Logan; A H Love; M Marsh; C J Mulder; K Sjoberg; L Stenhammer; J Walker-Smith; A M Marossy; R S Houlston Journal: J Med Genet Date: 1999-09 Impact factor: 6.318
Authors: Penny L Post; Matthew J Tyska; Christopher B O'Connell; Kimberly Johung; Amanda Hayward; Mark S Mooseker Journal: J Biol Chem Date: 2002-01-18 Impact factor: 5.157
Authors: Karen A Hunt; Dermot P B McGovern; Parveen J Kumar; Subrata Ghosh; Simon P L Travis; Julian R F Walters; Derek P Jewell; Raymond J Playford; David A van Heel Journal: Eur J Hum Genet Date: 2005-04 Impact factor: 4.246
Authors: Alienke J Monsuur; Paul I W de Bakker; Behrooz Z Alizadeh; Alexandra Zhernakova; Marianna R Bevova; Eric Strengman; Lude Franke; Ruben van't Slot; Martine J van Belzen; Ineke C M Lavrijsen; Begoña Diosdado; Mark J Daly; Chris J J Mulder; M Luisa Mearin; Jos W R Meijer; Gerrit A Meijer; Erica van Oort; Martin C Wapenaar; Bobby P C Koeleman; Cisca Wijmenga Journal: Nat Genet Date: 2005-11-13 Impact factor: 38.330
Authors: John M Russo; Peter Florian; Le Shen; W Vallen Graham; Maria S Tretiakova; Alfred H Gitter; Randall J Mrsny; Jerrold R Turner Journal: Gastroenterology Date: 2005-04 Impact factor: 22.682
Authors: Michael Economou; Thomas A Trikalinos; Konstantinos T Loizou; Epameinondas V Tsianos; John P A Ioannidis Journal: Am J Gastroenterol Date: 2004-12 Impact factor: 10.864
Authors: Anu Kemppinen; Minna Suvela; Pentti J Tienari; Irina Elovaara; Keijo Koivisto; Tuula Pirttilä; Mauri Reunanen; Ilkka Rautakorpi; Jan Hillert; Frida Lundmark; Annette Oturai; Lars Ryder; Hanne F Harbo; Elisabeth G Celius; Aarno Palotie; Mark Daly; Leena Peltonen; Janna Saarela Journal: Eur J Hum Genet Date: 2009-01-14 Impact factor: 4.246
Authors: Barbara Chladkova; Jana Kamanova; Lenka Palova-Jelinkova; Jana Cinova; Peter Sebo; Ludmila Tuckova Journal: J Cell Mol Med Date: 2011-04 Impact factor: 5.310