Polymorphisms of the macrophage migration inhibitory factor gene in a UK population with Type 1 diabetes mellitus

Abstract

Aims Macrophage migration inhibitory factor (MIF) is a potent pro-inflammatory cytokine whose production is transcriptionally regulated by glucose. Experimental data from both Type 1 diabetes mellitus (T1D) patients and animal models suggests a role for MIF in the development of T1D. The aim of this study was to employ gene resequencing to identify common DNA polymorphisms in the MIF gene and subsequently assess haplotype tagged single nucleotide polymorphisms (htSNPs) using a combination of case-control and family-based association analyses in order to assess the association of MIF htSNPs with the development of T1D in a white population.Methods All exons, introns and approximately 3 kb upstream and downstream of the MIF gene were screened for DNA polymorphisms in 46 individuals using DNA sequencing. Genotyping of the htSNPs was performed in 432 cases, 407 control subjects and 290 T1D parent-offspring trios, using Taqman, Sequenom, Pyrosequencing and fluorescence-based microsatellite technologies.Results Twenty-three polymorphisms (two novel) with a minor allele frequency > 10% were identified. Four MIF htSNPs (rs875643 G>A, rs7388067 C>T, rs5844572 ) ⁄ CATT, rs6003941 T>G) were identified. Allele and haplotype frequencies were similar between case and control groups (P > 0.6 by permutation test) and assessment of allele transmission distortion from informative parents to affected offspring also failed to find an association. Stratification of these analyses for age-at-onset and human leukocyte antigen (HLA)-DR risk group (DR3 ⁄ DR4) did not reveal any significant associations.Conclusions It is unlikely that common polymorphisms in the MIF gene strongly influence susceptibility to T1D in the UK population.

Genetic Variation in Macrophage Migration Inhibitory Factor Associated with Gestational Diabetes Mellitus and Metabolic Syndrome

“…Another investigation had demonstrated the association between MIF gene polymorphisms and infl ammatory disorders, both in development and severity [23,24] . Previous study suggested a possible role for MIF in glucose metabolism [25] , which leads to understand the increasing of MIF in response to serum glucose concentration [6,26] . Besides the anti-infl ammatory and immune response regulation, reducing MIF level might lead to improve the glucose pathway by decreasing peripheral insulin resistance [27] .…”

“…In this regard, macrophage migration inhibitory factor (MIF) may be one important candidate, which was confi rmed in a microarray study [5] . MIF gene, which is located on 22q11.2 position, is a small gene with 3 short exons and 2 introns [6,7] . MIF have a critical role in immune system and infl ammatory responses [6,8,9] .…”

“…MIF gene, which is located on 22q11.2 position, is a small gene with 3 short exons and 2 introns [6,7] . MIF have a critical role in immune system and infl ammatory responses [6,8,9] . The association between MIF with insulin resistance was reported by illustrating a signifi cant increase of circulating MIF in T2D compared to healthy indiThe aim of this study was to investigate the association of macrophage migration inhibitory factor (MIF) polymorphism rs1007888 with gestational diabetes mellitus (GDM), and its association with postpartum metabolic syndrome.…”

Association between macrophage migration inhibitory factor rs1007888 and GDM

“…The human MIF gene is located on chromosome 22 q11.2, and is present as a single gene copy composed of 3 exons and 2 introns (Herder et al, 2008a;Martin et al, 2010). MIF is a 115-amino acid protein with a relative molecular weight of 12.5 kDa.…”