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Effect of macrophage migration inhibitory factor (MIF) gene variants and MIF serum concentrations on the risk of type 2 diabetes: results from the MONICA/KORA Augsburg Case–Cohort Study, 1984–2002

2007; Springer Science+Business Media; Volume: 51; Issue: 2 Linguagem: Inglês

10.1007/s00125-007-0800-3

1432-0428

Christian Herder, N. Klopp, Jens Baumert, Martina Müller‐Nurasyid, Natalie Khuseyinova, Christa Meisinger, Stéphan Martin, Thomas Illig, Wolfgang Köenig, Barbara Thorand,

Nuclear Receptors and Signaling

Macrophage migration inhibitory factor (MIF) is a central mediator of innate immunity. Our aim was to investigate the triangular association between MIF genotypes, circulating MIF concentrations and incident type 2 diabetes, and to use a Mendelian randomisation approach to assess the causal role of MIF. Using a case–cohort design within the population-based MONICA/KORA Augsburg Study, based on 502 individuals with incident type 2 diabetes (293 men, 209 women) and 1,632 non-cases (859 men, 773 women), we determined MIF serum levels at baseline and genotyped four MIF single nucleotide polymorphisms (SNPs). The C allele of SNP rs1007888 (3.8 kb 3′ of the translation termination codon) was associated with increased circulating MIF. MIF genotype rs1007888CC was associated with an increased risk of type 2 diabetes in women [hazard ratio (95% CI) 1.74 (1.02–2.97)], but not in men [1.17 (0.75–1.81)]. Elevated MIF serum levels were associated with higher type 2 diabetes risk also only in women [HR (95% CI) 1.95 (1.15–3.29) comparing extreme quartiles after multiple adjustment], but not in men (p for interaction 0.039). The association between MIF levels and incident type 2 diabetes was significantly higher in obese women (111 cases, 147 non-cases) compared with non-obese women (98 cases, 626 non-cases; p for BMI interaction 0.0002). The consistent triangular relationship between genotypes, serum levels and incident type 2 diabetes in women indicates that MIF may play a causal role in the aetiology of type 2 diabetes and that elevated MIF levels confer a higher disease risk.