15 Citations (Scopus)

Abstract

BACKGROUND: Inflammatory bowel disease (IBD) is typically diagnosed at 20 to 40 years of age. However, very young versus elderly patients with IBD may have different mechanisms of disease that may affect prognosis and care. OBJECTIVES: The purpose of this work was to identify single nucleotide polymorphisms associated with age of onset of Crohn's disease and ulcerative colitis. DESIGN: Patients were genotyped using a custom microarray chip containing 332 IBD-associated single nucleotide polymorphisms. Age at diagnosis as a continuous variable was assessed using linear regression. Patients were then subgrouped by age at diagnosis and compared by the Fisher exact test. Bonferroni correction was used in all of the analyses. SETTINGS: This study was conducted at a tertiary academic hospital. PATIENTS: Sixty patients with Crohn's disease and 26 with ulcerative colitis were ≤16 years old, 259 patients with Crohn's disease and 248 with ulcerative colitis were 17-60 years old, and 10 patients with Crohn's disease and 20 with ulcerative colitis were >60 years old at diagnosis and included in this study. MAIN OUTCOME MEASURES: Age at diagnosis and single nucleotide polymorphism correlations were measured in this study. RESULTS: The NOD2 single nucleotide polymorphism rs2076756 was associated with younger age at Crohn's disease diagnosis (p = 0.0002). Patients with the AA/ wild-type genotype were diagnosed at 31.9 ± 1.23 years, AG heterozygotes at 25.6 ± 0.99 years, and GG/at-risk allele homozygotes at 22.6 ± 1.32 years. Depending on age categories compared, single nucleotide polymorphisms in POU5F1, TNFSF15, and HLA DRB1∗501 were associated with age of Crohn's disease diagnosis. No genetic associations were seen between ulcerative colitis and linear age at diagnosis; however, the G allele of the LAMB1 single nucleotide polymorphism rs886774 was found to be associated with ulcerative colitis diagnosed at ≤16 versus >17 years old (p = 0.008). LIMITATIONS: This study was limited to known IBD single nucleotide polymorphisms. CONCLUSIONS: This analysis reaffirms the association between NOD2, a molecule of innate immunity, and early Crohn's disease onset. This is the first report of a possible association between early Crohn's disease and the POU5F1, TNFSF15, and HLA DRB1∗501 genes. The LAMB1 gene, associated with mucosal basement membrane integrity, was associated with early onset ulcerative colitis and, thus, suggests a fundamentally different mechanism of early disease pathogenesis in ulcerative colitis versus Crohn's disease.

Original languageEnglish (US)
Pages (from-to)321-327
Number of pages7
JournalDiseases of the colon and rectum
Volume58
Issue number3
DOIs
StatePublished - Jan 1 2015

Fingerprint

Inflammatory Bowel Diseases
Crohn Disease
Ulcerative Colitis
Early Diagnosis
Single Nucleotide Polymorphism
Alleles
Homozygote
Heterozygote
Age of Onset
Basement Membrane
Innate Immunity
Tertiary Care Centers
Genes
Linear Models
Genotype

All Science Journal Classification (ASJC) codes

  • Gastroenterology

Cite this

Connelly, Tara M. ; Berg, Arthur S. ; Iii, Leonard Harris ; Brinton, David ; Deiling, Sue ; Koltun, Walter A. / Genetic determinants associated with early age of diagnosis of IBD. In: Diseases of the colon and rectum. 2015 ; Vol. 58, No. 3. pp. 321-327.
@article{2a18aa6dc59245b5bd11823e91c6aabb,
title = "Genetic determinants associated with early age of diagnosis of IBD",
abstract = "BACKGROUND: Inflammatory bowel disease (IBD) is typically diagnosed at 20 to 40 years of age. However, very young versus elderly patients with IBD may have different mechanisms of disease that may affect prognosis and care. OBJECTIVES: The purpose of this work was to identify single nucleotide polymorphisms associated with age of onset of Crohn's disease and ulcerative colitis. DESIGN: Patients were genotyped using a custom microarray chip containing 332 IBD-associated single nucleotide polymorphisms. Age at diagnosis as a continuous variable was assessed using linear regression. Patients were then subgrouped by age at diagnosis and compared by the Fisher exact test. Bonferroni correction was used in all of the analyses. SETTINGS: This study was conducted at a tertiary academic hospital. PATIENTS: Sixty patients with Crohn's disease and 26 with ulcerative colitis were ≤16 years old, 259 patients with Crohn's disease and 248 with ulcerative colitis were 17-60 years old, and 10 patients with Crohn's disease and 20 with ulcerative colitis were >60 years old at diagnosis and included in this study. MAIN OUTCOME MEASURES: Age at diagnosis and single nucleotide polymorphism correlations were measured in this study. RESULTS: The NOD2 single nucleotide polymorphism rs2076756 was associated with younger age at Crohn's disease diagnosis (p = 0.0002). Patients with the AA/ wild-type genotype were diagnosed at 31.9 ± 1.23 years, AG heterozygotes at 25.6 ± 0.99 years, and GG/at-risk allele homozygotes at 22.6 ± 1.32 years. Depending on age categories compared, single nucleotide polymorphisms in POU5F1, TNFSF15, and HLA DRB1∗501 were associated with age of Crohn's disease diagnosis. No genetic associations were seen between ulcerative colitis and linear age at diagnosis; however, the G allele of the LAMB1 single nucleotide polymorphism rs886774 was found to be associated with ulcerative colitis diagnosed at ≤16 versus >17 years old (p = 0.008). LIMITATIONS: This study was limited to known IBD single nucleotide polymorphisms. CONCLUSIONS: This analysis reaffirms the association between NOD2, a molecule of innate immunity, and early Crohn's disease onset. This is the first report of a possible association between early Crohn's disease and the POU5F1, TNFSF15, and HLA DRB1∗501 genes. The LAMB1 gene, associated with mucosal basement membrane integrity, was associated with early onset ulcerative colitis and, thus, suggests a fundamentally different mechanism of early disease pathogenesis in ulcerative colitis versus Crohn's disease.",
author = "Connelly, {Tara M.} and Berg, {Arthur S.} and Iii, {Leonard Harris} and David Brinton and Sue Deiling and Koltun, {Walter A.}",
year = "2015",
month = "1",
day = "1",
doi = "10.1097/DCR.0000000000000274",
language = "English (US)",
volume = "58",
pages = "321--327",
journal = "Diseases of the Colon and Rectum",
issn = "0012-3706",
publisher = "Lippincott Williams and Wilkins",
number = "3",

}

Genetic determinants associated with early age of diagnosis of IBD. / Connelly, Tara M.; Berg, Arthur S.; Iii, Leonard Harris; Brinton, David; Deiling, Sue; Koltun, Walter A.

In: Diseases of the colon and rectum, Vol. 58, No. 3, 01.01.2015, p. 321-327.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Genetic determinants associated with early age of diagnosis of IBD

AU - Connelly, Tara M.

AU - Berg, Arthur S.

AU - Iii, Leonard Harris

AU - Brinton, David

AU - Deiling, Sue

AU - Koltun, Walter A.

PY - 2015/1/1

Y1 - 2015/1/1

N2 - BACKGROUND: Inflammatory bowel disease (IBD) is typically diagnosed at 20 to 40 years of age. However, very young versus elderly patients with IBD may have different mechanisms of disease that may affect prognosis and care. OBJECTIVES: The purpose of this work was to identify single nucleotide polymorphisms associated with age of onset of Crohn's disease and ulcerative colitis. DESIGN: Patients were genotyped using a custom microarray chip containing 332 IBD-associated single nucleotide polymorphisms. Age at diagnosis as a continuous variable was assessed using linear regression. Patients were then subgrouped by age at diagnosis and compared by the Fisher exact test. Bonferroni correction was used in all of the analyses. SETTINGS: This study was conducted at a tertiary academic hospital. PATIENTS: Sixty patients with Crohn's disease and 26 with ulcerative colitis were ≤16 years old, 259 patients with Crohn's disease and 248 with ulcerative colitis were 17-60 years old, and 10 patients with Crohn's disease and 20 with ulcerative colitis were >60 years old at diagnosis and included in this study. MAIN OUTCOME MEASURES: Age at diagnosis and single nucleotide polymorphism correlations were measured in this study. RESULTS: The NOD2 single nucleotide polymorphism rs2076756 was associated with younger age at Crohn's disease diagnosis (p = 0.0002). Patients with the AA/ wild-type genotype were diagnosed at 31.9 ± 1.23 years, AG heterozygotes at 25.6 ± 0.99 years, and GG/at-risk allele homozygotes at 22.6 ± 1.32 years. Depending on age categories compared, single nucleotide polymorphisms in POU5F1, TNFSF15, and HLA DRB1∗501 were associated with age of Crohn's disease diagnosis. No genetic associations were seen between ulcerative colitis and linear age at diagnosis; however, the G allele of the LAMB1 single nucleotide polymorphism rs886774 was found to be associated with ulcerative colitis diagnosed at ≤16 versus >17 years old (p = 0.008). LIMITATIONS: This study was limited to known IBD single nucleotide polymorphisms. CONCLUSIONS: This analysis reaffirms the association between NOD2, a molecule of innate immunity, and early Crohn's disease onset. This is the first report of a possible association between early Crohn's disease and the POU5F1, TNFSF15, and HLA DRB1∗501 genes. The LAMB1 gene, associated with mucosal basement membrane integrity, was associated with early onset ulcerative colitis and, thus, suggests a fundamentally different mechanism of early disease pathogenesis in ulcerative colitis versus Crohn's disease.

AB - BACKGROUND: Inflammatory bowel disease (IBD) is typically diagnosed at 20 to 40 years of age. However, very young versus elderly patients with IBD may have different mechanisms of disease that may affect prognosis and care. OBJECTIVES: The purpose of this work was to identify single nucleotide polymorphisms associated with age of onset of Crohn's disease and ulcerative colitis. DESIGN: Patients were genotyped using a custom microarray chip containing 332 IBD-associated single nucleotide polymorphisms. Age at diagnosis as a continuous variable was assessed using linear regression. Patients were then subgrouped by age at diagnosis and compared by the Fisher exact test. Bonferroni correction was used in all of the analyses. SETTINGS: This study was conducted at a tertiary academic hospital. PATIENTS: Sixty patients with Crohn's disease and 26 with ulcerative colitis were ≤16 years old, 259 patients with Crohn's disease and 248 with ulcerative colitis were 17-60 years old, and 10 patients with Crohn's disease and 20 with ulcerative colitis were >60 years old at diagnosis and included in this study. MAIN OUTCOME MEASURES: Age at diagnosis and single nucleotide polymorphism correlations were measured in this study. RESULTS: The NOD2 single nucleotide polymorphism rs2076756 was associated with younger age at Crohn's disease diagnosis (p = 0.0002). Patients with the AA/ wild-type genotype were diagnosed at 31.9 ± 1.23 years, AG heterozygotes at 25.6 ± 0.99 years, and GG/at-risk allele homozygotes at 22.6 ± 1.32 years. Depending on age categories compared, single nucleotide polymorphisms in POU5F1, TNFSF15, and HLA DRB1∗501 were associated with age of Crohn's disease diagnosis. No genetic associations were seen between ulcerative colitis and linear age at diagnosis; however, the G allele of the LAMB1 single nucleotide polymorphism rs886774 was found to be associated with ulcerative colitis diagnosed at ≤16 versus >17 years old (p = 0.008). LIMITATIONS: This study was limited to known IBD single nucleotide polymorphisms. CONCLUSIONS: This analysis reaffirms the association between NOD2, a molecule of innate immunity, and early Crohn's disease onset. This is the first report of a possible association between early Crohn's disease and the POU5F1, TNFSF15, and HLA DRB1∗501 genes. The LAMB1 gene, associated with mucosal basement membrane integrity, was associated with early onset ulcerative colitis and, thus, suggests a fundamentally different mechanism of early disease pathogenesis in ulcerative colitis versus Crohn's disease.

UR - http://www.scopus.com/inward/record.url?scp=84928111661&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84928111661&partnerID=8YFLogxK

U2 - 10.1097/DCR.0000000000000274

DO - 10.1097/DCR.0000000000000274

M3 - Article

C2 - 25664710

AN - SCOPUS:84928111661

VL - 58

SP - 321

EP - 327

JO - Diseases of the Colon and Rectum

JF - Diseases of the Colon and Rectum

SN - 0012-3706

IS - 3

ER -