FUT2 nonsecretor status links type 1 diabetes susceptibility and resistance to infection.
OBJECTIVE
FUT2 encodes the α(1,2) fucosyltransferase that determines blood group secretor status. Homozygotes (A/A) for the common nonsense mutation rs601338A>G (W143X) are nonsecretors and are unable to express histo-blood group antigens in secretions and on mucosal surfaces. This mutation has been reported to provide resistance to Norovirus and susceptibility to Crohn's disease, and hence we aimed to determine if it also affects risk of type 1 diabetes.


METHODS
rs601338A>G was genotyped in 8,344 patients with type 1 diabetes, 10,008 control subjects, and 3,360 type 1 diabetic families. Logistic regression models were used to analyze the case-control collection, and conditional logistic regression was used to analyze the family collection. RESULTS The nonsecretor A/A genotype of rs601338A>G was found to confer susceptibility to type 1 diabetes in both the case-control and family collections (odds ratio for AA 1.29 [95% CI 1.20-1.37] and relative risk for AA 1.22 [95% CI = 1.12-1.32]; combined P = 4.3 × 10(-18)), based on a recessive effects model.


CONCLUSIONS
Our findings linking FUT2 and type 1 diabetes highlight the intriguing relationship between host resistance to infections and susceptibility to autoimmune disease.
Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
Deborah J
DJ
Smyth
Jason D
JD
Cooper
Joanna M M
JM
Howson
Pamela
P
Clarke
Kate
K
Downes
Trupti
T
Mistry
Helen
H
Stevens
Neil M
NM
Walker
John A
JA
Todd
D000017:ABO Blood-Group System / Q000276:immunology / Q000378:metabolism*; D001208:Asia; D012634:Bodily Secretions / Q000378:metabolism*; D016022:Case-Control Studies; D018389:Codon, Nonsense; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology; D060467:Disease Resistance; D005060:Europe; D005192:Family Health; D005260:Female; D005647:Fucosyltransferases / Q000235:genetics*; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D007239:Infections / Q000276:immunology*; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D009656:North America; D000097631:Galactoside 2-alpha-L-fucosyltransferase
D000017:ABO Blood-Group System; D018389:Codon, Nonsense; D005647:Fucosyltransferases; D007527:Isoenzymes; D000097631:Galactoside 2-alpha-L-fucosyltransferase