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Fucosyltransferase 2 (FUT2) non-secretor status is associated with Crohn's disease.
Tuesday,2012-11-06 12:19 America/Los_Angeles — eenright
| Title | Fucosyltransferase 2 (FUT2) non-secretor status is associated with Crohn's disease. |
| Publication Type | Journal Article |
| Year of Publication | 2010 |
| Authors | McGovern, DPB, Jones, MR, Taylor, KD, Marciante, K, Yan, X, Dubinsky, M, Ippoliti, A, Vasiliauskas, E, Berel, D, Derkowski, C, Dutridge, D, Fleshner, P, Shih, DQ, Melmed, G, Mengesha, E, King, L, Pressman, S, Haritunians, T, Guo, X, Targan, SR, Rotter, JI |
| Corporate/Institutional Authors | International IBD Genetics Consortium, |
| Journal | Hum Mol Genet |
| Volume | 19 |
| Issue | 17 |
| Pagination | 3468-76 |
| Date Published | 2010 Sep 01 |
| ISSN | 1460-2083 |
| Keywords | Adolescent, Adult, Aged, Child, Child, Preschool, Cohort Studies, Crohn Disease, Female, Fucosyltransferases, Genome-Wide Association Study, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Young Adult |
| Abstract | <p>Genetic variation in both innate and adaptive immune systems is associated with Crohn's disease (CD) susceptibility, but much of the heritability to CD remains unknown. We performed a genome-wide association study (GWAS) in 896 CD cases and 3204 healthy controls all of Caucasian origin as defined by multidimensional scaling. We found supportive evidence for 21 out of 40 CD loci identified in a recent CD GWAS meta-analysis, including two loci which had only nominally achieved replication (rs4807569, 19p13; rs991804, CCL2/CCL7). In addition, we identified associations with genes involved in tight junctions/epithelial integrity (ASHL, ARPC1A), innate immunity (EXOC2), dendritic cell biology [CADM1 (IGSF4)], macrophage development (MMD2), TGF-beta signaling (MAP3K7IP1) and FUT2 (a physiological trait that regulates gastrointestinal mucosal expression of blood group A and B antigens) (rs602662, P=3.4x10(-5)). Twenty percent of Caucasians are 'non-secretors' who do not express ABO antigens in saliva as a result of the FUT2 W134X allele. We demonstrated replication in an independent cohort of 1174 CD cases and 357 controls between the four primary FUT2 single nucleotide polymorphisms (SNPs) and CD (rs602662, combined P-value 4.90x10(-8)) and also association with FUT2 W143X (P=2.6x10(-5)). Further evidence of the relevance of this locus to CD pathogenesis was demonstrated by the association of the original four SNPs and CD in the recently published CD GWAS meta-analysis (rs602662, P=0.001). These findings strongly implicate this locus in CD susceptibility and highlight the role of the mucus layer in the development of CD.</p> |
| DOI | 10.1093/hmg/ddq248 |
| Alternate Journal | Hum. Mol. Genet. |
| PubMed ID | 20570966 |
| PubMed Central ID | PMC2916706 |
| Grant List | M01-RR00425 / RR / NCRR NIH HHS / United States U01 DK062413 / DK / NIDDK NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States N01-HC-85086 / HC / NHLBI NIH HHS / United States N01-HC-35129 / HC / NHLBI NIH HHS / United States N01 HC-55222 / HC / NHLBI NIH HHS / United States N01-HC-75150 / HC / NHLBI NIH HHS / United States N01 HC-15103 / HC / NHLBI NIH HHS / United States DK 063491 / DK / NIDDK NIH HHS / United States N01-HC-45133 / HC / NHLBI NIH HHS / United States N01-HC-85079 / HC / NHLBI NIH HHS / United States R01 HL087652 / HL / NHLBI NIH HHS / United States P01-DK046763 / DK / NIDDK NIH HHS / United States DK062413 / DK / NIDDK NIH HHS / United States DK084554 / DK / NIDDK NIH HHS / United States DK76984 / DK / NIDDK NIH HHS / United States |