与腰臀比相关的新基因座在脂肪组织中的特异性 mRNA 表达。
Fat depot-specific mRNA expression of novel loci associated with waist-hip ratio.
机构信息
Interdisciplinary Centre for Clinical Research, Medical Faculty, University of Leipzig, Leipzig, Germany.
1] Department of Internal Medicine, Neurology, and Dermatology, Clinic for Endocrinology and Nephrology, University Clinic of Leipzig, Leipzig, Germany [2] IFB AdiposityDiseases, University of Leipzig, Leipzig, Germany.
出版信息
Int J Obes (Lond). 2014 Jan;38(1):120-5. doi: 10.1038/ijo.2013.56. Epub 2013 Apr 19.
OBJECTIVE
We hypothesized that genes within recently identified loci associated with waist-hip ratio (WHR) exhibit fat depot-specific mRNA expression, which correlates with obesity-related traits.
METHODS
Adipose tissue (AT) mRNA expression of 6 genes (TBX15/WARS2, STAB1, PIGC, ZNRF3 and GRB14) within these loci showing coincident cis-expression quantitative trait loci was measured in 222 paired samples of human visceral (vis) and subcutaneous (sc) AT. The relationship of mRNA expression levels with obesity-related quantitative traits was assessed by Pearson's correlation analyses. Multivariate linear relationships were assessed by generalized linear regression models.
RESULTS
Whereas only PIGC, ZNFR3 and STAB1 mRNA expression in sc AT correlated nominally with WHR (P<0.05, adjusted for age and sex), mRNA expression of all studied genes in at least one of the fat depots correlated significantly with vis and/or sc fat area (P ranging from 0.05 to 4.0 × 10(6), adjusted for age and sex). Consistently, the transcript levels of WARS, PIGC and GRB14 were nominally associated with body mass index (BMI) (P ranging from 0.02 to 9.2 × 10(5), adjusted for age and sex). Moreover, independent of sex, obesity and diabetes status, differential expression between vis and sc AT was observed for all tested genes (P<0.01). Finally, the rs10195252 T-allele was nominally associated with increased GRB14 sc mRNA expression (P=0.025 after adjusting for age, sex and BMI).
CONCLUSIONS
Our data including the inter-depot variability of mRNA expression suggests that genes within the WHR-associated loci might be involved in the regulation of fat distribution.
目的
我们假设与腰臀比（WHR）相关的最近确定的基因座内的基因表现出脂肪组织特异性 mRNA 表达，与肥胖相关特征相关。
方法
在 222 对人体内脏（vis）和皮下（sc）脂肪组织的配对样本中，测量了这些基因座内的 6 个基因（TBX15/WARS2、STAB1、PIGC、ZNRF3 和 GRB14）的脂肪组织（AT）mRNA 表达，这些基因的顺式表达数量性状基因座具有一致性。通过 Pearson 相关分析评估 mRNA 表达水平与肥胖相关定量特征之间的关系。通过广义线性回归模型评估多变量线性关系。
结果
虽然只有 sc AT 中的 PIGC、ZNFR3 和 STAB1 mRNA 表达与 WHR 呈名义相关（P<0.05，年龄和性别调整），但至少在一个脂肪组织中研究的所有基因的 mRNA 表达与 vis 和/或 sc 脂肪面积显著相关（P 范围为 0.05 至 4.0×10（6），年龄和性别调整）。一致地，WARS、PIGC 和 GRB14 的转录水平与体重指数（BMI）名义相关（P 范围为 0.02 至 9.2×10（5），年龄和性别调整）。此外，独立于性别、肥胖和糖尿病状态，在所有测试的基因中观察到 vis 和 sc AT 之间的差异表达（P<0.01）。最后，rs10195252T-等位基因与 GRB14 sc mRNA 表达增加名义相关（调整年龄、性别和 BMI 后 P=0.025）。
结论
我们的数据包括 mRNA 表达的隔室变异性，表明与 WHR 相关的基因座内的基因可能参与脂肪分布的调节。
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