Type

Journal Article

Authors

P Ronan O'Connell
Kieran Sheahan
Desmond C. Winter
John Hyland
Hugh Mulcahy
Diarmuid O'Donoghue
Denise Keegan
Glen A Doherty
Gráinne Lennon
Robert M O'Connell
and 1 others

Subjects

Biochemistry

Topics
male connective tissue growth factor recurrence age of onset ctgf protein human phenotype retrospective studies adult humans smad3 protein human surgery smad3 protein genotype crohn disease female genetics polymorphism single nucleotide

The influence of CTGF single-nucleotide polymorphisms on outcomes in Crohn's disease. (2013)

Abstract To examine the association between single-nucleotide polymorphisms (SNPs) in CTGF (connective tissue growth factor) and patient outcomes after terminal ileal resection for Crohn's disease. The primary indication for intestinal resection in Crohn's disease is fibrostenotic terminal ileal disease. CTGF is a cytokine overexpressed in the intestine of patients with Crohn's disease that influences outcomes in other disease processes. DNA was extracted from formalin-fixed, paraffin-embedded tissue from 147 patients with Crohn's disease who had undergone terminal ileal resection between 1981 and 2009. Genotyping was performed for 4 CTGF SNPs (rs9402373, rs12526196, rs6918698, and rs9399005), which modulate nuclear factor binding and CTGF production, and a smad3 SNP (rs17293632) involved in the CTGF pathway. Patients were phenotyped using the Montreal Disease Classification. Sixty-seven of 147 patients (45.6%) were male; the mean age at diagnosis was 30.3 ± 12.6 years and the mean follow-up duration was 8.3 ± 7.1 years. Genotype-phenotype analysis demonstrated that the rs6918698GG genotype was associated with an older age of disease onset [>40 years; 30.6% vs 13.2%; odds ratio (OR): 2.891; 95% confidence interval (CI): 1.170-7.147). The rs9402373CC genotype was positively associated with type B1 disease (50.7% vs 26.3%; OR: 2.876; 95% CI: 1.226-6.743) and negatively associated with B2 disease (37.0% vs 65.0%; OR: 0.317; 95% CI: 0.144-0.699). None of the 5 SNPs assessed influenced clinical or surgical recurrence of Crohn's disease after intestinal resection. On multivariate analysis, male sex odds ratio (OR): 0.235; 95% CI: 0.073-0.755; P = 0.015] and never having smoked tobacco (OR: 0.249; 95% CI: 0.070-0.894; P = 0.033) reduced the risk, whereas having a prior appendectomy increased the risk (OR: 5.048; 95% CI: 1.632-15.617; P = 0.005) of surgical recurrence. These data implicate the rs6918698GG genotype with an age of disease onset of greater than 40 years in Crohn's disease whereas the rs9402373CC genotype is associated with a nonstricturing, nonpenetrating disease phenotype. CTGF SNPs do not influence the rate of recurrence after terminal ileal resection for Crohn's disease.
Collections Ireland -> University College Dublin -> PubMed

Full list of authors on original publication

P Ronan O'Connell, Kieran Sheahan, Desmond C. Winter, John Hyland, Hugh Mulcahy, Diarmuid O'Donoghue, Denise Keegan, Glen A Doherty, Gráinne Lennon, Robert M O'Connell and 1 others

Experts in our system

1
P R O'Connell
University College Dublin
Total Publications: 75
 
2
Kieran Sheahan
University College Dublin
Total Publications: 40
 
3
Desmond C. Winter
University College Dublin
Total Publications: 53
 
4
John Hyland
Dublin Business School
Total Publications: 47
 
5
Hugh E Mulcahy
University College Dublin
Total Publications: 43
 
6
Diarmuid O'Donoghue
University College Dublin
Total Publications: 42
 
7
Denise Keegan
University College Dublin
Total Publications: 22
 
8
Glen A Doherty
University College Dublin
Total Publications: 57
 
9
Grainne Lennon
University of Limerick