Dopaminergic genetic contributions to obesity in kidney transplant recipients

University Of Tennessee Health Sci Ctr, Memphis TN

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Abstract

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.