Metallothionein genes: no association with Crohn's disease in a New Zealand population

Inflammatory bowel disease (IBD) is a disorder characterised by chronic, relapsing inflammation of the gastrointestinal tract and is characterized by the presence of an increased level of reactive oxygen species in the mucosal intestinal tissue as well as oxidative DNA and protein damage, defective host-microbe interactions, immune cell infiltration, and disturbed T cell apoptosis. Metallothioneins (MTs) are able to affect all of these processes, making them good candidates for IBD. MTs are ubiquitous metal-binding proteins that have been highly conserved throughout evolution and are rapidly upregulated in response to an inflammatory stimulus. There are four main isoforms expressed in humans: MT1 (subtypes A, B, E, F, G, H, M, X), MT2, MT3 and MT4. These genes cluster together on a single locus on chromosome 16 (16q13) [1].Support for the hypothesis of MTs playing an important role in the pathogenesis of IBD has come from various reports demonstrating altered MT expression in IBD. However these reports have been contradictory (for a summary see Waeytens et al., 2009 [2]) with some studies reporting MT upregulation in IBD [3,4] and others demonstrating a downregulation [5-11]. The inconsistencies between the various studies may be explained by differences in patients samples such as age, medication, disease activity, zinc status, as well as from where the tissue was sampled (ileum or colon).Whilst there have been several studies investigating expression of MTs in IBD, there have been no studies published to date investigating genetic variants in MTs and IBD. The aim of this study is to identify SNPs across these genes and to genotype these in a well-characterised Caucasian New Zealand IBD dataset and to examine the results for evidence of genetic association between any of the MT genes and IBD.A total of 1044 subjects from New Zealand were included in the study: 406 CD patients and 638 age and sex matched controls. All participants self-reported European ancestry.Cli