Nephrology, Queen's University of Belfast, Belfast, UK.
Diabet Med. 2010 Feb;27(2):143-9. doi: 10.1111/j.1464-5491.2009.02916.x.
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.
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.
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.
It is unlikely that common polymorphisms in the MIF gene strongly influence susceptibility to T1D in the UK population.
巨噬细胞移动抑制因子（MIF）是一种强效的促炎细胞因子，其产生受葡萄糖转录调控。来自 1 型糖尿病（T1D）患者和动物模型的实验数据表明，MIF 在 T1D 的发展中起作用。本研究旨在通过基因重测序鉴定 MIF 基因中的常见 DNA 多态性，随后使用病例对照和家系关联分析相结合的方法评估 MIF htSNP 与 T1D 发展的关联，以评估 MIF htSNP 在白人人群中与 T1D 发展的关联。
使用 DNA 测序在 46 个人中筛选 MIF 基因的所有外显子、内含子和大约 3 kb 上下游的 DNA 多态性。使用 Taqman、Sequenom、Pyrosequencing 和荧光基于微卫星技术对 432 例病例、407 例对照和 290 例 T1D 父母-子女三胞胎进行 htSNP 基因分型。
确定了 23 个多态性（2 个新的），其次要等位基因频率> 10%。鉴定出 4 个 MIF htSNP（rs875643 G>A、rs7388067 C>T、rs5844572- / CATT、rs6003941 T>G）。病例组和对照组之间的等位基因和单倍型频率相似（通过置换检验 P>0.6），并且从信息父母到受影响子女的等位基因传递偏斜的评估也未发现关联。对这些分析进行年龄发病和人类白细胞抗原（HLA）-DR 风险组（DR3/DR4）的分层也没有发现任何显著关联。
MIF 基因中的常见多态性不太可能强烈影响英国人群对 T1D 的易感性。
