Contribution of the NOD1/CARD4 insertion/deletion polymorphism +32656 to inflammatory bowel disease in Northern Europe

J. van Limbergen; R. K. Russell; E. R. Nimmo; L. Törkvist; C. W. Lees; H. E. Drummond; L. Smith; N. H. Anderson; P. M. Gillett; P. McGrogan; K. Hassan; L. T. Weaver; W. M. Bisset; G. Mahdi; I. D. Arnott; U. Sjöqvist; M. Lördal; S. M. Farrington; M. G. Dunlop; D. C. Wilson; Jack Satsangi

doi:https://doi.org/10.1002/ibd.20124

Contribution of the NOD1/CARD4 insertion/deletion polymorphism +32656 to inflammatory bowel disease in Northern Europe

J. van Limbergen, R. K. Russell, E. R. Nimmo, L. Törkvist, C. W. Lees, H. E. Drummond, L. Smith, N. H. Anderson, P. M. Gillett, P. McGrogan, K. Hassan, L. T. Weaver, W. M. Bisset, G. Mahdi, I. D. Arnott, U. Sjöqvist, M. Lördal, S. M. Farrington, M. G. Dunlop, D. C. WilsonJack Satsangi

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Background: NOD1/CARD4 and NOD2/CARD15 are both intracellular pattern-recognition receptors. The NOD1/CARD4 gene lies within a previously described inflammatory bowel disease (IBD) locus (7p14). An association has been suggested between the NOD1/CARD4+32656 deletion*1 variant of a complex deletion*1/insertion*2 polymorphism and IBD in 1 recent study in Europe. Our aim was to assess the influence of NOD1/CARD4+32656 on disease susceptibility and phenotype in the Scottish and Swedish IBD populations. Methods: A total of 3,962 individuals (1,791 IBD patients, 522 parents, 1,649 healthy controls) from 2 independent populations (Scotland and Sweden) were genotyped for NOD1/CARD4+32656 A/C by TaqMan and direct sequencing. Case-control, Transmission Disequilibrium Testing (TDT) and detailed genotype-phenotype (Montreal) analyses were performed. The case-control analysis had 80% power to detect an effect size of odds ratio (OR) 1.21 for IBD. Results: In case-control analyses in Scottish and Swedish patients, none of the genotypes studied in IBD, Crohn's disease (CD) or ulcerative colitis (UC), differed significantly from controls (deletion*1 allelic frequency 73.9%, 73.6%, 73.9%, and 73.6%, respectively: all P > 0.8). No epistatic interaction with NOD2/CARD15 was seen for CD susceptibility. TDT analysis in our Scottish early onset cohort was negative. Conclusions: This variant allele of NOD1/CARD4+32656 is not associated with a strong effect on susceptibility to IBD in children and adults in Northern Europe. A gene-wide haplotype-based approach may be preferable to analysis of individual variants to assess the contribution of the NOD1/CARD4 gene to IBD. Copyright © 2007 Crohn's & Colitis Foundation of America, Inc.

Original language	English
Pages (from-to)	882-889
Journal	Inflammatory Bowel Diseases
Volume	13
Issue number	7
DOIs	https://doi.org/10.1002/ibd.20124
Publication status	Published - Jul 2007
Externally published	Yes

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van Limbergen, J., Russell, R. K., Nimmo, E. R., Törkvist, L., Lees, C. W., Drummond, H. E., Smith, L., Anderson, N. H., Gillett, P. M., McGrogan, P., Hassan, K., Weaver, L. T., Bisset, W. M., Mahdi, G., Arnott, I. D., Sjöqvist, U., Lördal, M., Farrington, S. M., Dunlop, M. G., ... Satsangi, J. (2007). Contribution of the NOD1/CARD4 insertion/deletion polymorphism +32656 to inflammatory bowel disease in Northern Europe. Inflammatory Bowel Diseases, 13(7), 882-889. https://doi.org/10.1002/ibd.20124

@article{51b15a93d073411ab5014f49dbd9f492,

title = "Contribution of the NOD1/CARD4 insertion/deletion polymorphism +32656 to inflammatory bowel disease in Northern Europe",

abstract = "Background: NOD1/CARD4 and NOD2/CARD15 are both intracellular pattern-recognition receptors. The NOD1/CARD4 gene lies within a previously described inflammatory bowel disease (IBD) locus (7p14). An association has been suggested between the NOD1/CARD4+32656 deletion*1 variant of a complex deletion*1/insertion*2 polymorphism and IBD in 1 recent study in Europe. Our aim was to assess the influence of NOD1/CARD4+32656 on disease susceptibility and phenotype in the Scottish and Swedish IBD populations. Methods: A total of 3,962 individuals (1,791 IBD patients, 522 parents, 1,649 healthy controls) from 2 independent populations (Scotland and Sweden) were genotyped for NOD1/CARD4+32656 A/C by TaqMan and direct sequencing. Case-control, Transmission Disequilibrium Testing (TDT) and detailed genotype-phenotype (Montreal) analyses were performed. The case-control analysis had 80% power to detect an effect size of odds ratio (OR) 1.21 for IBD. Results: In case-control analyses in Scottish and Swedish patients, none of the genotypes studied in IBD, Crohn's disease (CD) or ulcerative colitis (UC), differed significantly from controls (deletion*1 allelic frequency 73.9%, 73.6%, 73.9%, and 73.6%, respectively: all P > 0.8). No epistatic interaction with NOD2/CARD15 was seen for CD susceptibility. TDT analysis in our Scottish early onset cohort was negative. Conclusions: This variant allele of NOD1/CARD4+32656 is not associated with a strong effect on susceptibility to IBD in children and adults in Northern Europe. A gene-wide haplotype-based approach may be preferable to analysis of individual variants to assess the contribution of the NOD1/CARD4 gene to IBD. Copyright {\textcopyright} 2007 Crohn's & Colitis Foundation of America, Inc.",

author = "{van Limbergen}, J. and Russell, {R. K.} and Nimmo, {E. R.} and L. T{\"o}rkvist and Lees, {C. W.} and Drummond, {H. E.} and L. Smith and Anderson, {N. H.} and Gillett, {P. M.} and P. McGrogan and K. Hassan and Weaver, {L. T.} and Bisset, {W. M.} and G. Mahdi and Arnott, {I. D.} and U. Sj{\"o}qvist and M. L{\"o}rdal and Farrington, {S. M.} and Dunlop, {M. G.} and Wilson, {D. C.} and Jack Satsangi",

year = "2007",

month = jul,

doi = "https://doi.org/10.1002/ibd.20124",

language = "English",

volume = "13",

pages = "882--889",

journal = "Inflammatory Bowel Diseases",

issn = "1078-0998",

publisher = "John Wiley and Sons Inc.",

number = "7",

}

van Limbergen, J, Russell, RK, Nimmo, ER, Törkvist, L, Lees, CW, Drummond, HE, Smith, L, Anderson, NH, Gillett, PM, McGrogan, P, Hassan, K, Weaver, LT, Bisset, WM, Mahdi, G, Arnott, ID, Sjöqvist, U, Lördal, M, Farrington, SM, Dunlop, MG, Wilson, DC & Satsangi, J 2007, 'Contribution of the NOD1/CARD4 insertion/deletion polymorphism +32656 to inflammatory bowel disease in Northern Europe', Inflammatory Bowel Diseases, vol. 13, no. 7, pp. 882-889. https://doi.org/10.1002/ibd.20124

TY - JOUR

T1 - Contribution of the NOD1/CARD4 insertion/deletion polymorphism +32656 to inflammatory bowel disease in Northern Europe

AU - van Limbergen, J.

AU - Russell, R. K.

AU - Nimmo, E. R.

AU - Törkvist, L.

AU - Lees, C. W.

AU - Drummond, H. E.

AU - Smith, L.

AU - Anderson, N. H.

AU - Gillett, P. M.

AU - McGrogan, P.

AU - Hassan, K.

AU - Weaver, L. T.

AU - Bisset, W. M.

AU - Mahdi, G.

AU - Arnott, I. D.

AU - Sjöqvist, U.

AU - Lördal, M.

AU - Farrington, S. M.

AU - Dunlop, M. G.

AU - Wilson, D. C.

AU - Satsangi, Jack

PY - 2007/7

Y1 - 2007/7

N2 - Background: NOD1/CARD4 and NOD2/CARD15 are both intracellular pattern-recognition receptors. The NOD1/CARD4 gene lies within a previously described inflammatory bowel disease (IBD) locus (7p14). An association has been suggested between the NOD1/CARD4+32656 deletion*1 variant of a complex deletion*1/insertion*2 polymorphism and IBD in 1 recent study in Europe. Our aim was to assess the influence of NOD1/CARD4+32656 on disease susceptibility and phenotype in the Scottish and Swedish IBD populations. Methods: A total of 3,962 individuals (1,791 IBD patients, 522 parents, 1,649 healthy controls) from 2 independent populations (Scotland and Sweden) were genotyped for NOD1/CARD4+32656 A/C by TaqMan and direct sequencing. Case-control, Transmission Disequilibrium Testing (TDT) and detailed genotype-phenotype (Montreal) analyses were performed. The case-control analysis had 80% power to detect an effect size of odds ratio (OR) 1.21 for IBD. Results: In case-control analyses in Scottish and Swedish patients, none of the genotypes studied in IBD, Crohn's disease (CD) or ulcerative colitis (UC), differed significantly from controls (deletion*1 allelic frequency 73.9%, 73.6%, 73.9%, and 73.6%, respectively: all P > 0.8). No epistatic interaction with NOD2/CARD15 was seen for CD susceptibility. TDT analysis in our Scottish early onset cohort was negative. Conclusions: This variant allele of NOD1/CARD4+32656 is not associated with a strong effect on susceptibility to IBD in children and adults in Northern Europe. A gene-wide haplotype-based approach may be preferable to analysis of individual variants to assess the contribution of the NOD1/CARD4 gene to IBD. Copyright © 2007 Crohn's & Colitis Foundation of America, Inc.

AB - Background: NOD1/CARD4 and NOD2/CARD15 are both intracellular pattern-recognition receptors. The NOD1/CARD4 gene lies within a previously described inflammatory bowel disease (IBD) locus (7p14). An association has been suggested between the NOD1/CARD4+32656 deletion*1 variant of a complex deletion*1/insertion*2 polymorphism and IBD in 1 recent study in Europe. Our aim was to assess the influence of NOD1/CARD4+32656 on disease susceptibility and phenotype in the Scottish and Swedish IBD populations. Methods: A total of 3,962 individuals (1,791 IBD patients, 522 parents, 1,649 healthy controls) from 2 independent populations (Scotland and Sweden) were genotyped for NOD1/CARD4+32656 A/C by TaqMan and direct sequencing. Case-control, Transmission Disequilibrium Testing (TDT) and detailed genotype-phenotype (Montreal) analyses were performed. The case-control analysis had 80% power to detect an effect size of odds ratio (OR) 1.21 for IBD. Results: In case-control analyses in Scottish and Swedish patients, none of the genotypes studied in IBD, Crohn's disease (CD) or ulcerative colitis (UC), differed significantly from controls (deletion*1 allelic frequency 73.9%, 73.6%, 73.9%, and 73.6%, respectively: all P > 0.8). No epistatic interaction with NOD2/CARD15 was seen for CD susceptibility. TDT analysis in our Scottish early onset cohort was negative. Conclusions: This variant allele of NOD1/CARD4+32656 is not associated with a strong effect on susceptibility to IBD in children and adults in Northern Europe. A gene-wide haplotype-based approach may be preferable to analysis of individual variants to assess the contribution of the NOD1/CARD4 gene to IBD. Copyright © 2007 Crohn's & Colitis Foundation of America, Inc.

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=34547620484&origin=inward

UR - https://www.ncbi.nlm.nih.gov/pubmed/17285593

U2 - https://doi.org/10.1002/ibd.20124

DO - https://doi.org/10.1002/ibd.20124

M3 - Article

C2 - 17285593

SN - 1078-0998

VL - 13

SP - 882

EP - 889

JO - Inflammatory Bowel Diseases

JF - Inflammatory Bowel Diseases

IS - 7

ER -

Contribution of the NOD1/CARD4 insertion/deletion polymorphism +32656 to inflammatory bowel disease in Northern Europe

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