Tejero M E, Voruganti V S, Proffitt J M, Curran J E, Göring H H H, Johnson M P, Dyer T D, Jowett J B, Collier G R, Moses E K, MacCluer J W, Mahaney M C, Blangero J, Comuzzie A G, Cole S A
Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX, USA.
Heredity (Edinb). 2008 Jul;101(1):60-6. doi: 10.1038/hdy.2008.28. Epub 2008 Apr 30.
Resistin has been associated with inflammation and risk for cardiovascular disease. We previously reported evidence of a QTL on chromosome 19p13 affecting the abundance of resistin (RETN) mRNA in the omental adipose tissue of baboons (L0D score 3.8). In this study, whole genome transcription levels were assessed in human lymphocyte samples from 1240 adults participating in the San Antonio Family Heart Study, using the Sentrix Human-6 Expression Beadchip. Lymphocytes were surveyed, as it has been proposed that their expression levels may reflect those in harder to ascertain tissues, such as adipose tissue, that are thought to be more directly relevant to disease procesn was conducted to detect loci affecting RETN mRNA levels. We obtained significant evidence for a QTL influencing the RETN expression (LOD score 10.7) on chromosome 19p. This region is orthologous/homologous to the region previously localized on baboon chromosome 19. The strongest positional candidate gene in this region is the structural gene for resistin, itself. We also found evidence for a QTL influencing resistin protein levels (LOD score 5.3) on chromosome 14q. This differs from our previously reported QTL on chromosome 18 in baboons. The different QTLs for circulating protein suggests that post-translational processing and turnover may be influenced by different or multiple genes in baboons and humans. The parallel findings of a cis-eQTL for RETN mRNA in baboon omental tissue and human lymphocytes lends support to the strategy of using lymphocyte gene expression levels as a surrogate for gene expression levels in other tissues.
抵抗素与炎症及心血管疾病风险相关。我们之前报道了在狒狒网膜脂肪组织中，19号染色体短臂13区存在一个影响抵抗素（RETN）mRNA丰度的数量性状基因座（LOD值为3.8）的证据。在本研究中，使用Sentrix Human-6表达微珠芯片，对参与圣安东尼奥家族心脏研究的1240名成年人的人类淋巴细胞样本中的全基因组转录水平进行了评估。之所以对淋巴细胞进行检测，是因为有人提出其表达水平可能反映那些难以确定的组织（如脂肪组织）中的表达水平，而脂肪组织被认为与疾病过程更直接相关。进行了一项检测影响RETN mRNA水平基因座的研究。我们获得了19号染色体短臂上一个影响RETN表达的数量性状基因座的显著证据（LOD值为10.7）。该区域与先前在狒狒19号染色体上定位的区域是直系同源/同源的。该区域中最强的位置候选基因就是抵抗素自身的结构基因。我们还发现了14号染色体长臂上一个影响抵抗素蛋白水平的数量性状基因座的证据（LOD值为5.3）。这与我们之前报道的狒狒18号染色体上的数量性状基因座不同。循环蛋白的不同数量性状基因座表明，翻译后加工和周转可能受狒狒和人类中不同或多个基因的影响。狒狒网膜组织和人类淋巴细胞中RETN mRNA顺式表达数量性状基因座的平行发现，支持了将淋巴细胞基因表达水平用作其他组织中基因表达水平替代指标的策略。
