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Background & Aims: Recent studies reported a role for more than 70 genes or loci in the susceptibility to Crohn's disease (CD). However, the impact of these associations in clinical practice remains to be defined. The aim of the study was to analyse the relationship between genotypes and phenotypes for the main 53 CD-associated polymorphisms. Method: A cohort of 798 CD patients with a median follow up of 7 years was recruited by tertiary adult and paediatric gastroenterological centres. A detailed phenotypic description of the disease was recorded, including clinical presentation, response to treatments and complications. The participants were genotyped for 53 CD-associated variants previously reported in the literature and correlations with clinical sub-phenotypes were searched for. A replication cohort consisting of 722 CD patients was used to further explore the putative associations. Results: The NOD2 rare variants were associated with an earlier age at diagnosis (p = 0.0001) and an ileal involvement (OR = 2.25[1.49-3.41] and 2.77 [1.71-4.50] for rs2066844 and rs2066847, respectively). Colonic lesions were positively associated with the risk alleles of IL23R rs11209026 (OR = 2.25 [1.13-4.51]) and 6q21 rs7746082 (OR = 1.60 [1.10-2.34] and negatively associated with the risk alleles of IRGM rs13361189 (OR = 0.29 [0.11-0.74]) and DEFB1 rs11362 (OR = 0.50 [0.30- 0.80]). The ATG16L1 and IRGM variants were associated with a non-inflammatory behaviour (OR = 1.75 [1.22-2.53] and OR = 1.50 [1.04-2.16] respectively). However, these associations lost significance after multiple testing corrections. The protective effect of the IRGM risk allele on colonic lesions was the only association replicated in the second cohort (p = 0.03). Conclusions: It is not recommended to genotype the studied polymorphisms in routine practice. [ABSTRACT FROM AUTHOR]

OBJECTIVES:Anti-Saccharomyces cerevisiae antibodies (ASCAs) are present in 50–60% of patients with Crohn's disease (CD) and in 20–25% of their healthy relatives (HRs). The yeast, Candida albicans, has been shown to generate ASCAs, but the presence of C. albicans in the digestive tract of CD patients and their HRs has never been investigated. Therefore, we studied C. albicans carriage in familial CD and its correlation with ASCAs.METHODS:Study groups consisted of 41 CD families composed of 129 patients and 113 HRs, and 14 control families composed of 76 individuals. Mouth swabs and stool specimens were collected for isolation, identification, and quantification of yeasts. Serum samples were collected for detection of ASCAs and anti-C. albicans mannan antibodies (ACMAs).RESULTS:C. albicans was isolated significantly more frequently from stool samples from CD patients (44%) and their HRs (38%) than from controls (22%) (P<0.05). The prevalence of ACMAs was similar between CD patients, their HRs, and controls (22, 19, and 21%, respectively, P=0.845), whereas the prevalence of ASCAs was significantly increased in CD families (72 and 34% in CD and HRs, respectively, in contrast to 4% in controls, P<0.0001). AMCA levels correlated with C. albicans colonization in all populations. ASCA levels correlated with C. albicans colonization in HRs but not in CD patients.CONCLUSIONS:CD patients and their first-degree HRs are more frequently and more heavily colonized by C. albicans than are controls. ASCAs correlate with C. albicans colonization in HRs but not in CD. In HRs, ASCAs could result from an altered immune response to C. albicans. In CD, a subsequent alteration in sensing C. albicans colonization could occur with disease onset.Am J Gastroenterol 2009; 104:1745–1753; doi:10.1038/ajg.2009.225; published online 26 May 2009 [ABSTRACT FROM AUTHOR]