What question did this study set out to answer?

To determine whether sequence variations in the human melanocortin-4 receptor (MC4-R) gene contribute to obesity by identifying variants and evaluating their functional effects in vitro.

March 1, 1999Diabetes

Identification and functional analysis of novel human melanocortin-4 receptor variants.

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Authors

WGWei GuColumbia University ZTZhiguang TuHuazhong Agricultural University PKPatrick W. KleynHeart Rhythm Society

Discussion

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Implication

Genetic screening reveals functional melanocortin-4 receptor mutations in severe obesity, indicating coding variants are an uncommon cause of population obesity.

Key Points

To determine whether sequence variations in the human melanocortin-4 receptor (MC4-R) gene contribute to obesity by identifying variants and evaluating their functional effects in vitro.
Screened the MC4-R coding sequence for polymorphisms in 190 individuals selected on the basis of obesity status.
Cloned and expressed identified MC4-R allelic variants in vitro to assess ligand binding affinity and intracellular signaling compared with wild-type receptors.
Identified three allelic variants across the cohort, including two novel missense mutations: Thr112Met and Ile137Thr.
Demonstrated that the Ile137Thr variant, isolated from an individual with extreme obesity (BMI 57), exhibits severe impairment in both ligand binding and receptor signaling.
Observed a very low overall frequency of functionally disruptive mutations, indicating that MC4-R coding sequence polymorphism is unlikely to be a common cause of obesity in the general population.

Cite This Study

Gu et al. (1999) studied this question.

synapsesocial.com/papers/6aa17447b90bc0e4d272df22 https://doi.org/10.2337/diabetes.48.3.635

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March 1, 1999Diabetes

Identification and functional analysis of novel human melanocortin-4 receptor variants.

View Full Paper

Ask AI

Bookmark

Authors

WGWei GuColumbia University ZTZhiguang TuHuazhong Agricultural University PKPatrick W. KleynHeart Rhythm Society

Discussion

Member takes

Implication

Genetic screening reveals functional melanocortin-4 receptor mutations in severe obesity, indicating coding variants are an uncommon cause of population obesity.

Key Points

To determine whether sequence variations in the human melanocortin-4 receptor (MC4-R) gene contribute to obesity by identifying variants and evaluating their functional effects in vitro.
Screened the MC4-R coding sequence for polymorphisms in 190 individuals selected on the basis of obesity status.
Cloned and expressed identified MC4-R allelic variants in vitro to assess ligand binding affinity and intracellular signaling compared with wild-type receptors.
Identified three allelic variants across the cohort, including two novel missense mutations: Thr112Met and Ile137Thr.
Demonstrated that the Ile137Thr variant, isolated from an individual with extreme obesity (BMI 57), exhibits severe impairment in both ligand binding and receptor signaling.
Observed a very low overall frequency of functionally disruptive mutations, indicating that MC4-R coding sequence polymorphism is unlikely to be a common cause of obesity in the general population.

Cite This Study

Gu et al. (1999) studied this question.

synapsesocial.com/papers/6aa17447b90bc0e4d272df22 https://doi.org/10.2337/diabetes.48.3.635

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