The MYO9B gene is a strong risk factor for developing refractory celiac disease.
OBJECTIVE
Celiac disease (CD) is associated with HLA-DQ2 and HLA-DQ8 and has been linked to genetic variants in the MYO9B gene on chromosome 19. HLA-DQ2 homozygosity is associated with complications of CD such as refractory celiac disease type II (RCD II) and enteropathy-associated T-cell lymphoma (EATL). We investigated whether MYO9B also predisposes to RCD II and EATL.


METHODS
Genotyping of MYO9B and molecular HLA-DQ2 typing were performed on 62 RCD II and EATL patients, 421 uncomplicated CD patients, and 1624 controls.


RESULTS
One single nucleotide polymorphism in MYO9B showed a significantly different allele distribution in RCD II and EATL patients compared with controls (P = .00002). The rs7259292 T allele was significantly more frequent in RCD II and EATL patients compared with CD patients (P = .0003; odds ratio [OR], 3.61; 95% confidence interval [CI], 1.78-7.31). The frequency of the haplotype carrying the T allele of this single nucleotide polymorphism was significantly increased in RCD II and EATL patients (11%), compared with controls (2%) and CD patients (3%) (OR, 6.76; 95% CI, 3.40-13.46; P = 2.27E-09 and OR, 4.22; 95% CI, 1.95-9.11; P = .0001, respectively). Both MYO9B rs7259292 and HLA-DQ2 homozygosity increase the risk for RCD II and EATL to a similar extent when compared with uncomplicated CD patients (OR, 4.3; 95% CI, 1.9-9.8 and OR, 5.4; 95% CI, 3.0-9.6, respectively), but there was no evidence for any interaction between these 2 risk factors.


CONCLUSIONS
We show that both MYO9B and HLA-DQ2 homozygosity might be involved in the prognosis of CD and the chance of developing RCD II and EATL.
Wolters
Victorien M
VM
Department of Pediatric Gastroenterology, University Medical Centre Utrecht, Utrecht, The Netherlands.
Verbeek
Wieke H M
WH
Zhernakova
Alexandra
A
Onland-Moret
Charlotte
C
Schreurs
Marco W J
MW
Monsuur
Alienke J
AJ
Verduijn
Willem
W
Wijmenga
Cisca
C
Mulder
Chris J J
CJ
D000328:Adult; D000368:Aged; D000483:Alleles; D002446:Celiac Disease / Q000097:blood / Q000235:genetics*; D016001:Confidence Intervals; D004247:DNA / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006683:HLA-DQ Antigens / Q000097:blood / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009218:Myosins / Q000097:blood / Q000235:genetics*; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011379:Prognosis; D012307:Risk Factors
D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; C113469:myosin IXB; D004247:DNA; D009218:Myosins