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
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
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DOI：
10.1007/s00125-007-0800-3
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发表时间：
2008-02-01
期刊：
影响因子：
8.2
通讯作者：
Thorand, B.
中科院分区：
文献类型：
--
作者：
Herder, C.;Klopp, N.;Thorand, B.
目的/假设巨噬细胞迁移抑制因子（Macrophage migration inhibitory factor， MIF）是先天免疫的中枢调节因子。我们的目的是研究MIF基因型、循环MIF浓度和2型糖尿病发病率之间的三角关系，并使用孟德尔随机化方法评估MIF的因果作用。方法采用基于人群的MONICA/KORA Augsburg研究中的病例队列设计，基于502例2型糖尿病患者（293名男性，209名女性）和1632例非患者（859名男性，773名女性），我们确定了基线时的MIF血清水平，并对4个MIF单核苷酸多态性（snp）进行了基因分型。结果SNP rs1007888的C等位基因（翻译终止密码子3.8 kb 3′）与循环MIF增加有关。MIF基因型rs1007888CC与女性2型糖尿病风险增加相关[95% CI (95% CI) 1.74(1.02-2.97)]，但与男性无关[1.17(0.75-1.81)]。血清中MIF水平升高与2型糖尿病风险升高也仅在女性中相关[HR (95% CI) 1.95（1.15-3.29）比较多重调整后的极端四分位数]，但在男性中没有（相互作用p为0.039）。肥胖女性（111例，非147例）与非肥胖女性（98例，非626例；p为BMI相互作用0.0002）相比，MIF水平与2型糖尿病发病率之间的相关性显著更高。结论/解释基因型、血清水平和女性2型糖尿病发病率之间一致的三角关系表明，MIF可能在2型糖尿病的病因学中起因果作用，升高的MIF水平会导致更高的疾病风险。
Aims/hypothesis 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.Methods 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).Results 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).Conclusions/interpretation 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.