Contribution of higher risk genes and European admixture to Crohnʼs disease in African Americans
Autor: | Carmen Cuffari, Richard H. Duerr, Ming-Hsi Wang, Rick A. Kittles, Howard A. Kader, Toshihiko Okazaki, Kent D. Taylor, Judy H. Cho, Jean G. Ford, Geoffrey C. Nguyen, Michael Torbenson, Themistocles Dassopoulos, Kim L. Isaacs, Subra Kugathasan, Lisa W. Datta, Mary L. Harris, Steven R. Brant, Maria Oliva-Hemker, Stanley Hooker, Linda W. H. Kao, Duane T. Smoot, James D. Lewis, Yuqiong Wu, John D. Rioux, John F. Valentine, Mark S. Silverberg |
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Rok vydání: | 2012 |
Předmět: |
Adult
Male medicine.medical_specialty Genotype Population Nod2 Signaling Adaptor Protein Autophagy-Related Proteins Disease Polymorphism Single Nucleotide White People Article Crohn Disease GTP-Binding Proteins Risk Factors Polymorphism (computer science) Epidemiology medicine Humans Immunology and Allergy Genetic Predisposition to Disease education Gene Genetics education.field_of_study Crohn's disease business.industry Haplotype Gastroenterology Receptors Interleukin Inflammatory Bowel Diseases medicine.disease Black or African American Haplotypes Female Carrier Proteins business |
Zdroj: | Inflammatory Bowel Diseases. 18:2277-2287 |
ISSN: | 1078-0998 |
Popis: | African Americans (AAs) are an admixed population of West African (WA) and European ancestry (EA). Crohn's disease (CD) susceptibility genes have not been established. We therefore evaluated the contribution of European admixture and major established risk genes to AA CD.Ninety-seven admixture informative markers were genotyped for ancestry estimates using STRUCTURE. Overall, 354 AA CD cases and 354 ethnicity-matched controls were genotyped for total 21 single nucleotide polymorphisms (SNPs) in ATG16L1, NOD2, IBD5, IL23R and IRGM by TaqMan or direct sequencing. Association was evaluated by logistic regression, adjusted for ancestry.Mean EA was similar among the CD cases and controls (20.9% and 20.4%, respectively, P = 0.58). No significant admixture differences were observed among 211 to 227 cases stratified by phenotypic subclassifications including onset, surgery, site, and behavior. CD was associated with NOD2 carrier (6.93% CD, 2.15% Controls, P = 0.007), ATG16L1 Thr300Ala (36.1% CD, 29.3% Controls, P = 0.003), SLC22A4 and SLC22A5 (IBD5 locus) functional SNPs (Leu503Phe [10.5% CD, 7.6% Controls, P = 0.05] and g-207c [41.3% CD, 35.7% Controls, P = 0.03], respectively), and IL23R rs2201841 (18.2% CD, 13.8% Controls, P = 0.03), but not IRGM variants, nor three African ancestral NOD2 nonsynonymous variants. IBD5 risk was recessive. An all-minor allele IBD5 haplotype from EA was associated (P = 0.05), whereas a more common haplotype isolating g-207c was not.Specific functional gene variations contribute significantly to AA CD risk. Established NOD2, SLC22A4-A5, and ATG16L1 variants show increased CD risk, with IBD5 recessive. Although CD is more common in whites, European admixture is similar among AA cases and controls. |
Databáze: | OpenAIRE |
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