Genetic Association of Nonsynonymous Variants of the IL23R with Familial and Sporadic Inflammatory Bowel Disease in Women

Lin, Zhenwu; Poritz, Lisa S.; Franke, André; Li, Tong Yi; Ruether, Andreas; Byrnes, K; Wang, Yunhua; Gebhard, Anthony W.; MacNeill, Colin; Thomas, Neal J.; Schreiber, Stefan; Koltun, Walter A.

doi:10.1007/s10620-009-0782-8

Cited by 20 publications

(10 citation statements)

References 53 publications

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“…In addition, different races and ethnic groups have different degrees of susceptibility to IBD [5]. A number of studies have shown an association between IBD susceptibility and the nucleotide-binding oligomerization domain 2 gene ( NOD2, also known as CARD15 ), interleukin-23 receptor gene ( IL23r ), organic cation transporter novel type 1 gene ( OCTN1 ), and the intergenic region ( IGR ) variants [6-9]. NOD2 gene mutations have been extensively studied and described in the literature in terms of IBD susceptibility.…”

Section: Introductionmentioning

confidence: 99%

Clinical predictors of inflammatory bowel disease in a genetically well-defined Caucasian population

Kanaan

Eichenberger

Ahmad

et al. 2012

J Negat Results BioMed

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BackgroundCrohn's disease (CD) and ulcerative colitis (UC), the two main types of inflammatory bowel disease (IBD), are multifactorial conditions of unknown etiology. The objective of this study is to examine the combined gene-environment interactions influencing IBD susceptibility in a well-defined Caucasian cohort in rural mid-America.MethodsPatients were diagnosed to have CD or UC using conventional radiologic, endoscopic, and/or histopathologic findings. Histological diagnosis was made by a single specialist gastrointestinal pathologist with a particular interest in IBD. Information regarding cigarette smoke exposure was obtained by administration of the Behavioral Risk Factor Surveillance System Survey (BRFSS) to all patients. Genomic DNA was extracted from peripheral blood leukocytes, and polymerase chain reaction (PCR) amplification and genotyping were performed for 11 Single Nucleotide Polymorphisms (SNP) in NOD2, IL23r, OCTN1 genes along with IGR.ResultsOur cohort consists of 1196 patients: 435 controls, 485 CD patients, and 276 UC patients. Only patients with genotype data for at least 7 of 11 SNPs were included in our data analysis. The control groups for all 11 SNPs were in Hardy-Weinberg Equilibrium. In genotype-association SNP analysis, all NOD2 SNPs (rs5743293, rs2066844, rs2066845) and the IL23r SNP (rs11465804) showed a significant association to IBD (p < 0.03). A multiple gene-interaction analysis showed an association between NOD2 and IL23r with UC (p = 0.04). There were no associations between any OCTN1 and IGR SNPs and IBD in this cohort. A multivariable logistic regression analysis showed that female gender, "current" or "former" smoking status, family history of IBD, and NOD2 SNP minor alleles were associated with CD.ConclusionIBD remains to be challenging to properly diagnose, characterize, and treat. Our study proposes a combined genetic, phenotypic, and environmental approach in an attempt to better understand IBD. Previously demonstrated associations between OCTN1 and IGR and IBD were not confirmed.

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Section: Introductionmentioning

confidence: 99%

Clinical predictors of inflammatory bowel disease in a genetically well-defined Caucasian population

Kanaan

Eichenberger

Ahmad

et al. 2012

J Negat Results BioMed

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“…DNA amount and quality were measured by spectrophotometry. IL23R and ATG16L1 variants genotyping was performed using polymerase chain reaction (PCR) restriction fragment length polymorphism analysis (RFLP) as described respectively by Lin et al and Csöngei et al [10, 14]. …”

Section: Methodsmentioning

confidence: 99%

“…In Ulcerative colitis, the effect of this mutation seems to be insignificant [9]. In addition, Lin Z et al suggested the role of IL23R (L310P) as a protective polymorphism in UC females [10]. …”

Section: Introductionmentioning

confidence: 99%

IL23R and ATG16L1 variants in Moroccan patients with inflammatory bowel disease

et al. 2014

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BackgroundInflammatory bowel diseases (IBD) are chronic diseases of the gastrointestinal tract. Although their pathogenesis is unclear, the combination of genetic predisposition and environmental components are believed to be the main cause of these diseases. Recently, many variants in interleukin 23 receptor (IL23R) and autophagy-related 16-like 1 (ATG16L1) genes have been associated with the disease. Our objective was to assess the frequency of ATG16L1 (T300A) and IL23R (L310P) variants in Moroccan IBD (Crohn’s disease and Ulcerative Colitis) patients and to evaluate a possible effect of these variants on disease’s phenotype and clinical course.Methods96 Moroccan IBD patients and 114 unrelated volunteers were genotyped for ATG16L1 (T300A) and IL23R (L310P) variants by PCR-restriction fragment length polymorphism.ResultsThis is the first report on the prevalence of ATG16L1 (T300A) and IL23R (L310P) variants in a Moroccan group. We found that IL23R (L310P) variant conferred a protective effect for crohn’s disease (CD) but not ulcerative colitis (UC) patients. The presence of ATG16L1 (T300A) mutated alleles was associated with CD type but not with disease onset. In addition, the carriage of T300A variant alleles conferred a protective effect in UC.ConclusionOur results showed that the prevalence of ATG16L1 and IL23R variants was not significantly different between patients and controls. However a possible role of ATG16L1 (T300A) on CD phenotype was suggested.Electronic supplementary materialThe online version of this article (doi:10.1186/1756-0500-7-570) contains supplementary material, which is available to authorized users.

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“…The minor Q381 allele conferred approximately twofold greater protection against psoriasis and ankylosing spondylitis, and threefold protection against Crohn's disease [117]. Analysis from Lin and co-workers indicated a female specific protective effect of R381Q against Crohn's disease [118]. The polymorphism R381Q occurs at a frequency of 0-17% depending on the population [81].…”

Section: Molecular Analysis Of Disease-associated Il-23r Snpsmentioning

confidence: 99%

“…However, Lin and coworkers suggested L310P as a protective polymorphism in UC females. Furthermore, they examined the nsSNP Q3H (rs1884444) of IL23R, also located within exon 7, and observed no association with IBD [118]. heterozygous genotype showed impaired IL-23 induced T H 17 response [117].…”

Section: Molecular Analysis Of Disease-associated Il-23r Snpsmentioning

confidence: 99%