Association of DLG5 R30Q variant with inflammatory bowel disease

Daly, Mark J.; Pearce, Anna; Farwell, Lisa; Fisher, Sheila; Latiano, Anna; Prescott, Natalie J.; Forbes, Alastair; Mansfield, John C.; Sanderson, Jeremy; Langelier, Diane; Cohen, Albert; Bitton, Alain; Wild, Gary; Lewis, Cathryn M.; Annese,; Mathew, Christopher G.; Rioux, John D.

doi:10.1038/sj.ejhg.5201403

Cited by 68 publications

(48 citation statements)

References 14 publications

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“…Meanwhile, replication studies have emerged, but results are conflicting. Whereas Daly et al 47 was able to show independent replication in two cohorts from Quebec/ Italy and Quebec/UK, other recent studies were not able to show association. [48][49][50] More studies are inevitably needed to understand more about this gene.…”

Section: Current Status Of Genetics Research In Ibd S Vermeire and P mentioning

confidence: 79%

Current status of genetics research in inflammatory bowel disease

Vermeire¹,

Rutgeerts²

2005

Genes Immun

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The research on genetic susceptibility of inflammatory bowel diseases (IBD) has been tremendous and over 10 chromosomal regions have been identified by genome-wide scanning. Further fine mapping as well as candidate gene studies have already led to the identification of a number of susceptibility genes including CARD15, DLG5, OCTN1 and 2, NOD1, HLA, and TLR4. The CARD15 gene is undoubtedly replicated most widely and most understood at present. CARD15 is involved in the recognition of bacterial peptidoglycan-derived muramyl dipeptide (MDP) and will stimulate secretion of antimicrobial peptides including alpha-defensins (also called cryptdins) to protect the host from invasion. Genetic research in IBD has advanced our understanding of the clinical heterogeneity of the disease and has started to tackle the complex interactions between genetic risk factors and environmental risk factors in IBD. Genes also interfere with the metabolization of drugs and may influence the clinical response and the drug-related toxicity. Interesting pharmacogenetic data with respect to steroids, azathioprine, and infliximab have been generated in IBD. Overall, it is anticipated that genetic markers in the future will be implemented in an integrated molecular diagnostic and prognostic approach of our patients. Genes and Immunity (2005) 6, 637-645.

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Section: Current Status Of Genetics Research In Ibd S Vermeire and P mentioning

confidence: 79%

Current status of genetics research in inflammatory bowel disease

Vermeire¹,

Rutgeerts²

2005

Genes Immun

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“…The association of the R30Q variant with IBD has been supported in some studies [12,24,25,27], but failed to be replicated in others [28][29][30][31][32][33][34].…”

Section: Discussionmentioning

confidence: 99%

“…Stoll et al, [12] identified an IBD risk-associated DLG5 haplotype D that is uniquely distinguished by the 113A variant of R30Q. The association of R30Q with IBD has been replicated in other studies from several different patient populations [24][25][26]. Friedrichs et al, found a male-specific association of the R30Q variant with CD, with no association of the R30Q variant with women, nor with the entire sample of men and women [27].…”

Section: Introductionmentioning

confidence: 94%

Genetic Association of DLG5 R30Q with Familial and Sporadic Inflammatory Bowel Disease in Men

et al. 2009

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Abstract. Background:The association of DLG5 R30Q with IBD has been replicated in several populations, but is not statistically significant in others. We studied the incidence of DLG5 alleles in a population of IBD patients from Pennsylvania. Methods: DLG5 R30Q (rs1248696) and G1066G (rs1248634) were analyzed with PCR-based RFLP methods in a total of 521 subjects, that included 105 individuals with IBD and 139 without IBD from a familial IBD registry, 107 with sporadic IBD, and 170 unrelated healthy controls. R30Q was further analyzed with SNPlex TM Genotyping System in 473 samples. Results: RFLP genotyping data showed that, DLG5 R30Q was significantly associated with IBD overall (p = 0.006), and separately with CD (p = 0.009) and UC (p = 0.024). The association of R30Q with IBD was entirely due to a male-associated effect (male vs female p = 0.015 vs 0.241 (IBD), p = 0.024 vs 0.190 (CD), and p = 0.019 vs 0.575 (UC)). The frequency of the A allele carriage was elevated in both affected and unaffected members in the familial IBD cohort compared to healthy controls (p = 0.037). In the family pedigrees, we observed differences in the expression of IBD in individuals carrying the A allele between families. Conclusions: In the studied population, DLG5 R30Q was associated with all forms of IBD. An elevated presence of the R30Q variant was observed in all members of a familial IBD registry. This association of the R30Q variant with IBD was male-specific.

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“…Present approaches have not been able to discern whether these other genes or the class Ⅱ genes are the true risk genes in the HLA locus. [79][80][81][82] , multiple polymorphisms in the MDR1/ABCB1 gene on chromosome 7q [83][84][85][86][87][88][89][90][91][92] , and polymorphisms in the DLG5 gene on chromosome 10q [70,[93][94][95][96][97][98][99][100][101][102] . (See section C.4.1.)…”

Section: Hla Associationsmentioning

confidence: 99%

Inflammatory bowel disease: Genetic and epidemiologic considerations

Cho

2008

WJG

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Genome-wide association studies have firmly established that many genomic loci contribute to inflammatory bowel disease, especially in Crohn's disease. These studies have newly-established the importance of the interleukin 23 and autophagy pathways in disease pathogenesis. Future challenges include: (1) the establishment of precisely causal alleles, (2) definition of altered functional outcomes of associated and causal alleles and (3) integration of genetic findings with environmental factors.

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Association of DLG5 R30Q variant with inflammatory bowel disease

Cited by 68 publications

References 14 publications

Current status of genetics research in inflammatory bowel disease

Current status of genetics research in inflammatory bowel disease

Genetic Association of DLG5 R30Q with Familial and Sporadic Inflammatory Bowel Disease in Men

Inflammatory bowel disease: Genetic and epidemiologic considerations

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