The obesity-associated SNPs in intron 1 of the FTO gene affect primary transcript levels
The obesity-associated SNPs in intron 1 of the FTO gene affect primary transcript levels
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DOI：
10.1038/ejhg.2010.71
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发表时间：
2010-09-10
影响因子：
5.2
通讯作者：
Horsthemke, Bernhard
中科院分区：
文献类型：
--
作者：
Berulava, Tea;Horsthemke, Bernhard
如全基因组关联研究所示，FTO基因内含子1内的单核苷酸多态性（SNP）与体重指数和II型糖尿病相关，尽管这些SNP的功能意义尚不清楚。使用引物延伸分析，我们已经确定了等位基因FTO转录水平的比例在未剪接的异质核RNA制剂从个体的血液SNP rs 9939609杂合子。在SNP rs 4784319杂合和rs 9939609杂合或纯合的个体中研究相邻RPGRIP 1 L基因的等位基因表达比率。在5个个体中，含有rs 9939609的A（风险）等位基因的FTO转录本比含有T等位基因的FTO转录本更丰富（平均值1.38; 95%置信区间1.31-1.44）。在成纤维细胞样品中获得了类似的结果。我们还观察到倾斜等位基因表达的RPGRIP 1 L基因在血液中，但倾斜是独立的FTO基因型。我们的数据表明，FTO的表达增加与体重增加有关。European Journal of Human Genetics（2010）18，1054-1056; doi：10.1038/ejhg.2010.71; 2010年5月26日在线发表
As shown by genome-wide association studies single-nucleotide polymorphisms (SNPs) within intron 1 of the FTO gene are associated with the body mass index and type II diabetes, although the functional significance of these SNPs has remained unclear. Using primer extension assays, we have determined the ratio of allelic FTO transcript levels in unspliced heterogeneous nuclear RNA preparations from blood of individuals heterozygous for SNP rs9939609. Allelic expression ratios of the neighboring RPGRIP1L gene were investigated in individuals who were heterozygous for SNP rs4784319 and heterozygous or homozygous for rs9939609. In each of five individuals, the FTO transcripts containing the A (risk) allele of rs9939609 were more abundant than those with T allele (mean 1.38; 95% confidence interval 1.31-1.44). Similar results were obtained in a fibroblast sample. We also observed skewed allelic expression of the RPGRIP1L gene in blood, but skewing was independent of the FTO genotype. Our data suggest that increased expression of FTO is associated with increased body mass. European Journal of Human Genetics (2010) 18, 1054-1056; doi:10.1038/ejhg.2010.71; published online 26 May 2010