The MC4R p.Ile269Asn mutation confers a high risk for type 2 diabetes in the Mexican population via obesity dependent and independent effects

Vázquez‐Moreno, Miguel; Locia‐Morales, Daniel; Valladares‐Salgado, Adán; Sharma, Tanmay; Pérez‐Herrera, Aleyda; Gonzalez-Dzib, Roxana; Rodríguez-Ruíz, Francisco; Wacher, Niels H.; Cruz, Miguel; Meyre, David

doi:10.1038/s41598-021-82728-w

Cited by 6 publications

(9 citation statements)

References 34 publications

(45 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In addition to weight loss, patients showed decreased fat mass, lower fasting serum glucose levels and improved HOMA-IR measurements in both groups (Ile269Asn carriers and non-carriers). This is important considering that this mutation has been associated with an increased risk of type 2 diabetes in the Latino population [ 30 , 31 ]. Moreover, decreased plasma leptin and increased adiponectin levels may be explained by the weight loss and fat percentage decreases observed in phentermine-treated patients.…”

Section: Discussionmentioning

confidence: 99%

Effect of the Melanocortin 4-Receptor Ile269Asn Mutation on Weight Loss Response to Dietary, Phentermine and Bariatric Surgery Interventions

Salazar-Valencia

Villamil‐Ramírez

Barajas‐Olmos

et al. 2022

Genes

View full text Add to dashboard Cite

The loss of function melanocortin 4-receptor (MC4R) Ile269Asn mutation has been proposed as one of the most important genetic contributors to obesity in the Mexican population. However, whether patients bearing this mutation respond differently to weight loss treatments is unknown. We tested the association of this mutation with obesity in 1683 Mexican adults, and compared the response of mutation carriers and non-carriers to three different weight loss interventions: dietary restriction intervention, phentermine 30 mg/day treatment, and Roux-en-Y gastric bypass (RYGB) surgery. The Ile269Asn mutation was associated with obesity [OR = 3.8, 95% CI (1.5–9.7), p = 0.005]. Regarding interventions, in the dietary restriction group only two patients were MC4R Ile269Asn mutation carriers. After 1 month of treatment, both mutation carriers lost weight: −4.0 kg (−2.9%) in patient 1, and −1.8 kg (−1.5%) in patient 2; similar to the mean weight loss observed in six non-carrier subjects (−2.9 kg; −2.8%). Phentermine treatment produced similar weight loss in six carriers (−12.7 kg; 15.5%) and 18 non-carriers (−11.3 kg; 13.6%) after 6 months of pharmacological treatment. RYGB also caused similar weight loss in seven carriers (29.9%) and 24 non-carriers (27.8%), 6 months after surgery. Our findings suggest that while the presence of a single MC4R loss of function Ile269Asn allele significantly increases obesity risk, the presence of at least one functional MC4R allele seems sufficient to allow short-term weight loss in response to dietary restriction, phentermine and RYGB. Thus, these three different interventions may be useful for the short-term treatment of obesity in MC4R Ile269Asn mutation carriers.

show abstract

Section: Discussionmentioning

confidence: 99%

Effect of the Melanocortin 4-Receptor Ile269Asn Mutation on Weight Loss Response to Dietary, Phentermine and Bariatric Surgery Interventions

Salazar-Valencia

Villamil‐Ramírez

Barajas‐Olmos

et al. 2022

Genes

View full text Add to dashboard Cite

show abstract

“…26,27 Similarly, certain genes which are implicated in monogenic obesity also display variations which influence BMI and contribute to the risk of attaining polygenic obesity. [28][29][30][31] A heritable link to obesity is supported strongly across the literature, 22,23 although the effects of environment and lifestyle factors are also crucial clinically. Increased adiposity is produced by a homeostatic imbalance between calorific input and energy expenditure resulting in weight gain due to a positive net energy balance.…”

Section: Etiological Factors In Obesitymentioning

confidence: 98%

“…The use of GWAS technology has enabled greater pathophysiological understanding of polygenic obesity by delineating hundreds of novel polymorphisms which strongly influence BMI, although the current identities may explain a fraction of the total variance 26,27 . Similarly, certain genes which are implicated in monogenic obesity also display variations which influence BMI and contribute to the risk of attaining polygenic obesity 28–31 …”

Section: Etiological Factors In Obesitymentioning

confidence: 99%

Obesity and chronic kidney disease: A current review

Nawaz

Chinnadurai

Al-Chalabi

et al. 2022

Obesity Science & Practice

View full text Add to dashboard Cite

Background Obesity poses significant challenges to healthcare globally, particularly through its bi‐directional relationship with co‐morbid metabolic conditions such as type 2 diabetes and hypertension. There is also emerging evidence of an association between obesity and chronic kidney disease (CKD) which is less well characterized. Methods A literature search of electronic libraries was conducted to identify and present a narrative review of the interplay between obesity and CKD. Findings Obesity may predispose to CKD directly as it is linked to the histopathological finding of obesity‐related glomerulopathy and indirectly through its widely recognized complications such as atherosclerosis, hypertension, and type 2 diabetes. The biochemical and endocrine products of adipose tissue contribute to pathophysiological processes such as inflammation, oxidative stress, endothelial dysfunction, and proteinuria. The prevention and management of obesity may prove critical in counteracting both the development and advancement of CKD. Moreover, measures of abdominal adiposity such as waist circumference, are generally associated with worse morbidity and mortality in individuals receiving maintenance hemodialysis. Conclusion Obesity is a risk factor for the onset and progression of CKD and should be recognized as a potential target for a preventative public health approach to reduce CKD rates within the general population. Future research should focus on the use of glucagon‐like peptide‐1 receptor agonists and sodium–glucose cotransporter 2 inhibitors in patients with CKD and obesity due to their multi‐faceted actions on major outcomes.

show abstract

“…Collaborative studies are carried out at Specialty Hospital Clinical Epidemiology UIM and at Siglo XXI National Medical Center Biochemistry UIM in order to define obesity and diabetes molecular epidemiology in Mexico. Among them, collaborative studies with national and foreign institutions in which the association between single-nucleotide polymorphisms of certain genes, such as ABCA1 and MGEAS-14, and susceptibility to develop type 2 diabetes 2,28,29 , as well as the association between the melanocortin receptor gene 30,31 and the development of obesity have been identified in Mexican children and adults stand out. Currently, obesity and type 2 diabetes are considered pro-inflammatory conditions.…”

Section: Nutrition Metabolic Syndrome Obesity and Diabetesmentioning

confidence: 99%

Medical research at the Mexican Institute of Social Security: Seven decades of work, achievements, and challenges

Mercado¹,

Torres²,

Guerrero‐Romero³

et al. 2023

GMM

View full text Add to dashboard Cite

Since its foundation, more than 75 years ago, the Mexican Institute of Social Security (IMSS) has carried out multidisciplinary research -biomedical, clinical and epidemiological-focused on understanding and solving the medical problems that afflict its beneficiaries (more than 50% of the Mexican population). Initially, research was the result of individual and isolated efforts. In the 1960s, a small number of researchers formed the first research groups. Currently, 240 full-time scientists work at five centers and 40 research units located in different states of Mexico. In addition, approximately 270 doctors carry out clinical research at different primary, secondary and tertiary care units. During these seven decades, IMSS scientists have made relevant contributions to medicine, which have not only helped increase knowledge on the etiopathogenesis of numerous diseases, but also their diagnosis, prognosis and treatment. This article presents an overview of medical research carried out at IMSS, based on a historical approach and a review of some of the most relevant contributions in different fields of research.

show abstract

The MC4R p.Ile269Asn mutation confers a high risk for type 2 diabetes in the Mexican population via obesity dependent and independent effects

Cited by 6 publications

References 34 publications

Effect of the Melanocortin 4-Receptor Ile269Asn Mutation on Weight Loss Response to Dietary, Phentermine and Bariatric Surgery Interventions

Effect of the Melanocortin 4-Receptor Ile269Asn Mutation on Weight Loss Response to Dietary, Phentermine and Bariatric Surgery Interventions

Obesity and chronic kidney disease: A current review

Medical research at the Mexican Institute of Social Security: Seven decades of work, achievements, and challenges

Contact Info

Product

Resources

About