Association study of FUT2 (rs601338) with celiac disease and inflammatory bowel disease in the Finnish population.
Homozygosity for a nonsense mutation in the fucosyltransferase 2 (FUT2) gene (rs601338G>A) leads to the absence of ABH blood groups (FUT2 non-secretor status) in body fluids. As the secretor status has been shown to be a major determinant for the gut microbial spectrum, assumed to be important in the gut immune homeostasis, we studied the association of rs601338-FUT2 with celiac disease (CelD) and inflammatory bowel disease (IBD) in the Finnish population. Rs601338 was genotyped in CelD (n = 909), dermatitis herpetiformis (DH) (n = 116), ulcerative colitis (UC) (n = 496) and Crohn's disease (CD) (n = 280) patients and healthy controls (n = 2738). CelD showed significant genotypic [P = 0.0074, odds ratio (OR): 1.28] and recessive (P = 0.015, OR: 1.28) association with the rs601338-AA genotype. This was also found in the combined CelD+DH dataset (genotype association: P = 0.0060, OR: 1.28; recessive association: P < 0.011, OR: 1.28). The A allele of rs601338 showed nominal association with dominant protection from UC (P = 0.044, OR: 0.82) and UC+CD (P = 0.035, OR: 0.84). The frequency of non-secretors (rs601338-GG) in controls, CelD, DH, UC and CD datasets was 14.7%, 18%, 18.1%, 14.3% and 16.1%, respectively. No association was evident in the DH or CD datasets alone. In conclusion, FUT2 non-secretor status is associated with CelD susceptibility and FUT2 secretor status may also play a role in IBD in the Finnish population.
Research Program for Molecular Medicine and Department of Medical Genetics, Haartman Institute, University of Helsinki, Helsinki, Finland.
A S
AS
Parmar
N
N
Alakulppi
P
P
Paavola-Sakki
K
K
Kurppa
L
L
Halme
M
M
Färkkilä
U
U
Turunen
M
M
Lappalainen
K
K
Kontula
K
K
Kaukinen
M
M
Mäki
K
K
Lindfors
J
J
Partanen
P
P
Sistonen
J
J
Mättö
P
P
Wacklin
P
P
Saavalainen
E
E
Einarsdottir
D000483:Alleles; D001483:Base Sequence; D016022:Case-Control Studies; D002446:Celiac Disease / Q000201:enzymology* / Q000235:genetics*; D003093:Colitis, Ulcerative / Q000201:enzymology / Q000235:genetics; D003424:Crohn Disease / Q000201:enzymology / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D003874:Dermatitis Herpetiformis / Q000201:enzymology / Q000235:genetics; D005387:Finland; D005647:Fucosyltransferases / Q000235:genetics*; D005808:Genes, Recessive; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000201:enzymology* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D000097631:Galactoside 2-alpha-L-fucosyltransferase
D017931:DNA Primers; D005647:Fucosyltransferases; D000097631:Galactoside 2-alpha-L-fucosyltransferase