PDF(Pubmed)
Abstract：
In humans, the transient receptor potential vanilloid 1 (TRPV1) gene is activated by exogenous (e.g., high temperatures, irritating compounds such as capsaicin) and endogenous (e.g., endocannabinoids, inflammatory factors, fatty acid metabolites, low pH) stimuli. It has been shown to be involved in several processes including nociception, thermosensation, and energy homeostasis. In this study, we investigated the association between TRPV1 gene variants, sensory perception (to capsaicin and PROP), and body composition (BMI and bioimpedance variables) in human populations. By comparing sequences deposited in worldwide databases, we identified two haplotype blocks (herein referred to as H1 and H2) that show strong stabilizing selection signals (MAF approaching 0.50, Tajima\'s D > +4.5) only in individuals with sub-Saharan African ancestry. We therefore studied the genetic variants of these two regions in 46 volunteers of sub-Saharan descent and 45 Italian volunteers (both sexes). Linear regression analyses showed significant associations between TRPV1 diplotypes and body composition, but not with capsaicin perception. Specifically, in African women carrying the H1-b and H2-b haplotypes, a higher percentage of fat mass and lower extracellular fluid retention was observed, whereas no significant association was found in men. Our results suggest the possible action of sex-driven balancing selection at the non-coding sequences of the TRPV1 gene, with adaptive effects on water balance and lipid deposition.
摘要：
在人类中,瞬时受体电位香草酸1(TRPV1)基因被外源激活(例如，高温,刺激性化合物，如辣椒素)和内源性(例如，内源性大麻素，炎症因子，脂肪酸代谢物，低pH）刺激。它已被证明参与了几个过程，包括伤害感受，热感觉,和能量稳态。在这项研究中,我们调查了TRPV1基因变异之间的关联，感官知觉(对辣椒素和PROP)，和人群的身体成分（BMI和生物阻抗变量）。通过比较保存在全球数据库中的序列，我们确定了仅在撒哈拉以南非洲血统的个体中显示出强稳定选择信号(MAF接近0.50,Tajima'sD>+4.5)的两个单倍型区块(本文称为H1和H2).因此，我们在撒哈拉以南的46名志愿者和45名意大利志愿者（男女均为）中研究了这两个地区的遗传变异。线性回归分析显示TRPV1复型与身体成分之间存在显著关联，但不是辣椒素的感知。具体来说,在携带H1-b和H2-b单倍型的非洲妇女中，观察到较高的脂肪量百分比和较低的细胞外液潴留，而在男性中没有发现显著的关联。我们的结果表明，性别驱动的平衡选择可能在TRPV1基因的非编码序列中发挥作用，对水平衡和脂质沉积有适应性影响。
