Association of dopamine D2 receptor polymorphisms Ser311Cys and TaqIA with obesity or type 2 diabetes mellitus in Pima Indians

Jenkinson, CP; Hanson, Robert L.; Cray, Kimberly; Wiedrich, C; Wc, Knowler; Bogardus, Clifton; Baier, Leslie J.

doi:10.1038/sj.ijo.0801381

Cited by 55 publications

(45 citation statements)

References 27 publications

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“…However, the Ser311Cys mutation did not account for the linkage to BMI on chromosome 11 (14). Furthermore, in the smaller group of Pima Indians in the present study, we did not find differences in weight and percentage of body fat between genotypes (Tables 1 and 2).…”

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confidence: 36%

“…We have recently reported that among Pima Indians, individuals with a Cys311-encoding allele have a higher BMI than those homozygous for the Ser311-encoding allele (14). However, the Ser311Cys mutation did not account for the linkage to BMI on chromosome 11 (14).…”

mentioning

confidence: 99%

“…The Cys 311 variant of the human DRD2 has been shown to markedly impair the ability of the receptor to modulate adenylyl cyclase activity (6). Studies in genetically heterogeneous human populations have shown weak associations between DRD2 variants and obesity (7)(8)(9)(10)(11).We have previously observed that the location of DRD2 on chromosome 11q23-24 is near the peak of linkage of a locus known to influence type 2 diabetes, obesity, and energy expenditure in Pima Indians (12,13) and that individuals with a Cys311-encoding allele have a higher BMI than those homozygous for the Ser311-encoding allele (14). Therefore, the aim of the present study was to assess whether the Cys 311 variant of DRD2, a plausible candidate gene for obesity, promotes body weight gain by inhibiting energy expenditure in humans.…”

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confidence: 99%

“…Genotyping was done by Taqman allelic discrimination polymerase chain reaction using a model 7700 ABI Prism instrument (PE Applied Biosystems, Foster City, CA). The Ser311Cys polymorphism was typed as previously described (14). Two double-probe sets were used, at equal concentrations, to suppress a rare second His313His silent single nucleotide polymorphism (SNP) present just seven nucleotides downstream.…”

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A Ser311Cys Mutation in the Human Dopamine Receptor D2 Gene Is Associated With Reduced Energy Expenditure

et al. 2001

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Brain dopaminergic pathways play a major role in the control of movement. Absence of the murine dopamine D2 receptor gene (drd2) produces bradykinesia and hypothermia. A Ser311Cys mutation of the human DRD2 produces a marked functional impairment of the receptor and is associated with higher BMI in some populations. We hypothesized that the Ser311Cys mutation of DRD2 may inhibit energy expenditure. Here we report that total energy expenditure (doubly labeled water) measured in 89 nondiabetic Pima Indians was 244 kcal/ day lower in homozygotes for the Cys311-encoding allele when compared with those heterozygous and homozygous for the Ser311-encoding allele (P ‫؍‬ 0.056). The 24-h resting energy expenditure (respiratory chamber) measured in 320 nondiabetic Pimas was also 87 kcal/day lower in homozygotes for the Cys311-encoding allele when compared with those heterozygous and homozygous for the Ser311-encoding allele (P ‫؍‬ 0.026). These findings are the first evidence that a genetic mutation is associated with reduced energy expenditure in humans. Because the impact of this mutation on human obesity is small, we suggest that either the energy deficit induced is not large enough to significantly influence body weight in this population and/or that the Cys311-encoding allele is also associated with reduced energy intake. Diabetes 50:901-904, 2001

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A Ser311Cys Mutation in the Human Dopamine Receptor D2 Gene Is Associated With Reduced Energy Expenditure

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“…Individuals with genotypes containing either one or two copies of the A1 allele have fewer D2 receptors than have those lacking an A1 allele and so are associated with reduced brain dopamine signaling (Jonsson et al, 1999;Pohjalainen et al, 1998;Ritchie & Noble, 2003). In genetically homogeneous populations, such as the Pima Indians, a missense substitution in the DRD2 gene has been associated with reduced resting energy expenditure (Tataranni et al, 2001), greater BMI, and type II diabetes (Jenkinson et al, 2000). Epidemiological studies in genetically heterogeneous human populations have demonstrated a higher prevalence of the A1 DRD2 allele in obese individuals (~50%) compared with lean individuals (~30%; Blum et al, 1996;Comings et al, 1993;Comings, Gade, MacMurray, Muhleman, & Peters, 1996;Noble et al, 1994).…”

Section: Behavioral Genetics Of Food Reinforcementmentioning

confidence: 99%

Food reinforcement and eating: A multilevel analysis.

Epstein¹,

Leddy²,

Temple³

et al. 2007

Psychological Bulletin

319

323

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Eating represents a choice among many alternative behaviors. The purpose of this review is to provide an overview of how food reinforcement and behavioral choice theory are related to eating and to show how this theoretical approach may help organize research on eating from molecular genetics through treatment and prevention of obesity. Special emphasis is placed on how food reinforcement and behavioral choice theory are relevant to understanding excess energy intake and obesity and how they provide a framework for examining factors that may influence eating and are outside of those that may regulate energy homeostasis. Methods to measure food reinforcement are reviewed, along with factors that influence the reinforcing value of eating. Contributions of neuroscience and genetics to the study of food reinforcement are illustrated by using the example of dopamine. Implications of food reinforcement for obesity and positive energy balance are explored, with suggestions for novel approaches to obesity treatment based on the synthesis of behavioral and pharmacological approaches to food reinforcement. Keywords food reinforcement; food intake; choice; dopamine; behavioral genetics Choice is ubiquitous. There are many choices that people make that influence their eating and body weight, beginning with how early to get up, to exercise before breakfast or to sleep in, what to have for breakfast, and so on. These choices are made in the context of alternatives, many of which are pleasurable and exert considerable influence to do these behaviors rather than others. The morning is a good time for many people to choose to exercise, but a warm bed and a little extra sleep time represent a powerful alternative that even the most enthusiastic exerciser confronts and often succumbs to. Similarly, eating a good breakfast starts the day off right, but a pastry and coffee may be particularly inviting alternative foods that taste very good and may tempt many away from healthy cereal and fruit. This article provides a theoretical framework for understanding motivation to eat, how people make choices about eating versus engaging in other behaviors, and how these theoretical approaches can provide insights into obesity, mechanisms that regulate food choice, and implications of choice theory for interventions. One of the unique aspects of food reinforcement and behavioral theories of

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The Genetics of Human Obesity

Bouchard

Pérusse

2003

International Textbook of Diabetes Mellitus

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This chapter summarizes the research on the role of genetic variation in human obesity. It provides a brief review of our current understanding of the level of heritability and of the familial risk for increasing levels of excess body weight. Single‐gene defects known to cause obesity are discussed. The results of a large number of association studies performed with candidate genes are described. The candidate genes with at least five positive studies are highlighted. All published genomic scan studies relevant to obesity are reviewed, with an emphasis on the linkage results characterized by apparent convergence in at least two cohorts. Finally, the role of gene–environment interactions in the response to chronic positive or negative energy balance is examined.

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Association of dopamine D2 receptor polymorphisms Ser311Cys and TaqIA with obesity or type 2 diabetes mellitus in Pima Indians

Cited by 55 publications

References 27 publications

A Ser311Cys Mutation in the Human Dopamine Receptor D2 Gene Is Associated With Reduced Energy Expenditure

A Ser311Cys Mutation in the Human Dopamine Receptor D2 Gene Is Associated With Reduced Energy Expenditure

Food reinforcement and eating: A multilevel analysis.

The Genetics of Human Obesity

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