Transmission of CARD15 (NOD2) variants within families of patients with inflammatory bowel disease
| Autor: | Robert Vlietinck, Kristel Van Steen, Sofie Joossens, Severine Vermeire, Nele Esters, Greet Claessens, Paul Rutgeerts, Marie J. Pierik |
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| Rok vydání: | 2004 |
| Předmět: |
Adult
Male Heterozygote Adolescent Inheritance Patterns Nod2 Signaling Adaptor Protein Gene Expression Inflammatory bowel disease law.invention Cohort Studies Belgium Gene Frequency law NOD2 Prevalence Medicine Humans Genetic Predisposition to Disease Allele frequency Card15 nod2 Aged Aged 80 and over Hepatology business.industry Ileal Diseases digestive oral and skin physiology Gastroenterology Intracellular Signaling Peptides and Proteins Inflammatory Bowel Diseases Middle Aged medicine.disease Ulcerative colitis digestive system diseases Transmission (mechanics) Phenotype Immunology Mutation Female business Carrier Proteins Cohort study |
| Zdroj: | The American journal of gastroenterology. 99(2) |
| ISSN: | 0002-9270 |
| Popis: | Three single nucleotide polymorphisms (SNPs) in CARD15 have been independently associated with Crohn's disease (CD). Since nothing is known about the transmission of these variants within families, this was the subject of our study in Flemish patients with inflammatory bowel disease (IBD) and their healthy relatives.A cohort of 1,670 individuals (570 CD, 173 UC, 165 healthy controls, 762 first-degree unaffected relatives of CD patients) was genotyped for Arg702Trp, Gly908Arg, and Leu1007fsinsC. Mutant allele and carrier frequencies were compared between groups. Segregation patterns were compared using a bivariate Dale model.The carrier prevalence of CARD15 variants for CD patients was 46.3%, compared to 20.6% for healthy controls and 22.0% for ulcerative colitis (UC) patients (both p0.0001). An increased carriage rate of CARD15 variants was observed in unaffected relatives of CD patients (37.3%; p0.0001 vs controls), although this was significantly lower than in the CD patients (p = 0.001). Paternal transmission gave a 5.17-fold higher chance for the child to develop the disease compared to maternal transmission (95% CI [1.59, 16.78]; p = 0.0063). UC patients belonging to mixed IBD families carried significantly more mutations (42.3%) compared to other UC patients (18.4%) (p0.01).Maternal transmission of the CARD15 variant allele is associated with a lower proportion of affected individuals compared to paternal transmission. Therefore, maternal transmission does not carry an increased risk of transmission as does paternal transmission. The increased mutation carriage in unaffected siblings of CD patients and in UC patients belonging to mixed families suggests that other factors than CARD15 contribute to the eventual disease expression. |
| Databáze: | OpenAIRE |
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