Meta-Analysis
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World J Gastroenterol. Oct 21, 2013; 19(39): 6656-6664
Published online Oct 21, 2013. doi: 10.3748/wjg.v19.i39.6656
Macrophage migration inhibitory factor gene polymorphisms in inflammatory bowel disease: An association study in New Zealand Caucasians and meta-analysis
James D Falvey, Robert W Bentley, Tony R Merriman, Mark B Hampton, Murray L Barclay, Richard B Gearry, Rebecca L Roberts
James D Falvey, Robert W Bentley, Richard B Gearry, Murray L Barclay, Department of Medicine, University of Otago, Christchurch 8011, New Zealand
James D Falvey, Robert W Bentley, Richard B Gearry, Murray L Barclay, Department of Gastroenterology, Christchurch Hospital, Christchurch 8011, New Zealand
Tony R Merriman, Department of Biochemistry, University of Otago, Dunedin 9054, New Zealand
Mark B Hampton, Department of Pathology, University of Otago, Christchurch 8011, New Zealand
Rebecca L Roberts, Department of Surgical Sciences, Dunedin School of Medicine, Dunedin 9054, New Zealand
Author contributions: Falvey JD and Roberts RL contributed equally to this work; Falvey JD, Bentley RW, Hampton MB, Gearry RB, and Roberts RL designed the study; Roberts RL performed the genotyping of controls and patients; Merriman TR provided control subjects; Barclay ML and Gearry RB provided patients and associated phenotype data; Falvey JD and Roberts RL performed the data analyses and wrote the paper.
Supported by The Health Research Council of New Zealand; Scholarships from the Canterbury Gastroenterology Research Trust, New Zealand Society of Gastroenterology Ferring Scholarship, the Bowel and Liver Trust Canterbury and from the University of Otago to Falvey JD
Correspondence to: Dr. Rebecca L Roberts, Department of Surgical Sciences, Dunedin School of Medicine, 310 Great King St, PO Box 913, Dunedin 9054, New Zealand. rebecca.roberts@otago.ac.nz
Telephone: +64-3-4740999 Fax: +64-3-4747622
Received: February 12, 2013
Revised: April 5, 2013
Accepted: April 13, 2013
Published online: October 21, 2013
Abstract

AIM: To investigate the association of macrophage migration inhibitory factor (MIF) promoter polymorphisms with inflammatory bowel disease (IBD) risk.

METHODS: One thousand and six New Zealand Caucasian cases and 540 Caucasian controls were genotyped for the MIF SNP -173G > C (rs755622) and the repeat polymorphism CATT5-8 (rs5844572) using a pre-designed TaqMan SNP assay and capillary electrophoresis, respectively. Data were analysed for single site and haplotype association with IBD risk and phenotype. Meta-analysis was employed, to assess cumulative evidence of association of MIF -173G > C with IBD. All published genotype data for MIF -173G > C in IBD were identified using PubMed and subsequently searching the references of all PubMed-identified studies. Imputed genotypes for MIF -173G > C were generated from the Wellcome Trust Case Control Consortium (and National Institute of Diabetes and Digestive and Kidney Diseases). Separate meta-analyses were performed on Caucasian Crohn’s disease (CD) (3863 patients, 6031 controls), Caucasian ulcerative colitis (UC) (1260 patients, 1987 controls), and East Asian UC (416 patients and 789 controls) datasets using the Mantel-Haenszel method. The New Zealand dataset had 93% power, and the meta-analyses had 100% power to detect an effect size of OR = 1.40 at α = 0.05, respectively.

RESULTS: In our New Zealand dataset, single-site analysis found no evidence of association of MIF polymorphisms with overall risk of CD, UC, and IBD or disease phenotype (all P values > 0.05). Haplotype analysis found the CATT5/-173C haplotype occurred at a higher frequency in New Zealand controls compared to IBD patients (0.6 vs 0.01; P = 0.03, OR = 0.22; 95%CI: 0.05-0.99), but this association did not survive bonferroni correction. Meta-analysis of our New Zealand MIF -173G > C data with data from seven additional Caucasian datasets using a random effects model found no association of MIF polymorphisms with CD, UC, or overall IBD. Similarly, meta-analysis of all published MIF -173G > C data from East Asian datasets (416 UC patients, 789 controls) found no association of this promoter polymorphism with UC.

CONCLUSION: We found no evidence of association of MIF promoter polymorphisms with IBD.

Keywords: Crohn’s disease, Ulcerative colitis, Migration inhibitory factor, rs755622, rs5844572, Genetic association study

Core tip: Migration inhibitory factor (MIF) is an important mediator of inflammatory bowel disease (IBD). However, whether promoter polymorphisms in MIF alter susceptibility to IBD is unclear. This study sought to clarify this, as definitively as possible, for Caucasians and East Asians. Analysis of a New Zealand Caucasian cohort found no association of the polymorphisms MIF -173G > C and CATT5-8 with IBD. Subsequent meta-analysis of the New Zealand data with published MIF -173G > C data from other Caucasian cohorts found no association. A separate meta-analysis of East Asian datasets also found no evidence of association of this promoter polymorphism with IBD.