Dopaminergic genetic contributions to obesity in kidney transplant recipients

描述（由申请人提供）：肾移植受者是在移植后的第一年内很有可能增加大量体重（6至13公斤）的人群。然而，并不是所有的肾移植受者都会增加体重。研究发现，那些体重增加和不增加的人在身体活动和营养摄入方面几乎没有差异。免疫抑制药物也没有被证明在移植后体重增加中发挥实质性作用。这些观察结果表明，遗传因素可能在肾移植受者经历的体重增加差异中发挥作用。多巴胺是一种神经递质，以前与物质成瘾有关。最近，神经影像学和神经遗传学数据表明，多巴胺也可能在食物成瘾行为模型中发挥作用。多巴胺受体基因和与多巴胺活性相关的基因都与肥胖、体重增加和食物成瘾有关。在肾移植受者的皮下脂肪组织和血液中的初步基因表达研究已经证实，在这两种组织中，一些多巴胺能通路基因的表达与体重增加呈负相关。其中一些基因具有多态性，可能导致基因的活性改变，并使这些个体处于体重增加的风险中。这项研究的目的是确定与这些先前发现的多巴胺能基因相关的多态性在与肾移植人群体重增加的人口统计学特征相结合时是否具有预测价值。将使用真实的时间聚合酶链反应（RT-PCR）对先前收集的储存库白色血细胞样本进行这些多巴胺能多态性的基因分型。虽然我们没有看到移植后体重增加和不增加的患者之间的饮食有明显差异，但我们假设当患者被多巴胺能基因型分开时，饮食行为的变化可能会出现。这些信息，再加上患者如何应对他们的饮食欲望，他们在移植时的健康和体重状况，以及其他 环境因素可以解释肾移植后体重增加的现象。

DESCRIPTION (provided by applicant): Kidney transplant recipients are a population who experience a high likelihood of gaining a significant amount of weight (between 6 and 13 kilograms) in the first year after transplant. However, not all kidney transplant recipients gain weight. Studies have found little difference in physical activity and nutritional intake among those who do and do not gain weight. Immunosuppressant medications have also not been shown to play a substantive role in posttransplant weight gain. These observations suggest that genetic factors may have a role in the differential weight gain experienced by kidney transplant recipients. Dopamine is a neurotransmitter that has previously been implicated in substance addiction. Recently, neuroimaging and neurogenetic data have shown that dopamine may also play a role in models of food addiction behaviors. Both dopamine receptor genes and genes related to overall dopamine activity have been associated with obesity, weight gain, and food addiction. Preliminary gene expression studies in subcutaneous adipose tissue and blood of kidney transplant recipients have confirmed that expression of some dopaminergic pathway genes was negatively correlated with weight gain in these two tissues. Some of these genes have polymorphisms that may cause the genes' activity to be altered and place these individuals at risk for gaining weight. The purpose of the proposed study is to determine if polymorphisms associated with these previously found dopaminergic genes have predictive value when combined with demographic characteristics for weight gain in the kidney transplant population. Real time polymerase chain reaction (RT-PCR) will be used to genotype previously collected repository white blood cell samples for these dopaminergic polymorphisms. Although we have seen no gross differences in diet between patients who do and do not gain weight after transplant, we hypothesize that changes in dietary behavior may emerge when patients are separated by dopaminergic genotype. This information, when coupled with how patients respond to their dietary urges, their health and weight status at the time of transplant, and other environmental factors, could explain the weight gain phenomena seen following kidney transplantation.