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

Abstract We investigated the association between the loss-of-function mutation MC4R p.Ile269Asn and T2D risk in the Mexican population. We enrolled 6929 adults [3175 T2D cases and 3754 normal glucose tolerant (NGT) controls] and 994 NGT children in the study. Anthropometric data and T2D-related quan...

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Autores principales:	Miguel Vázquez-Moreno, Daniel Locia-Morales, Adan Valladares-Salgado, Tanmay Sharma, Aleyda Perez-Herrera, Roxana Gonzalez-Dzib, Francisco Rodríguez-Ruíz, Niels Wacher-Rodarte, Miguel Cruz, David Meyre
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1876f4c9831d41798d9cb65071b717a1
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spelling	oai:doaj.org-article:1876f4c9831d41798d9cb65071b717a12021-12-02T10:44:14ZThe MC4R p.Ile269Asn mutation confers a high risk for type 2 diabetes in the Mexican population via obesity dependent and independent effects10.1038/s41598-021-82728-w2045-2322https://doaj.org/article/1876f4c9831d41798d9cb65071b717a12021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82728-whttps://doaj.org/toc/2045-2322Abstract We investigated the association between the loss-of-function mutation MC4R p.Ile269Asn and T2D risk in the Mexican population. We enrolled 6929 adults [3175 T2D cases and 3754 normal glucose tolerant (NGT) controls] and 994 NGT children in the study. Anthropometric data and T2D-related quantitative traits were studied in 994 NGT children and 3754 NGT adults. The MC4R p.Ile269Asn mutation was genotyped using TaqMan. The MC4R p.Ile269Asn mutation was associated with T2D [OR = 2.00, 95% confidence interval (CI) 1.35–2.97, p = 0.00057] in Mexican adults. Additional adjustment for body-mass index (BMI) attenuated but did not remove the association (OR = 1.70, 95% CI 1.13–2.56, p = 0.011). The MC4R p.Ile269Asn mutation was associated with T2D (OR = 1.88, 95% CI 1.14–3.08, p = 0.013) in a subset of 1269 T2D cases and 1269 NGT controls matched for sex, age, and BMI. A mediation analysis estimated that BMI accounts for 22.7% of the association between MC4R p.Ile269Asn mutation and T2D risk (p = 4.55 × 10–6). An association was observed between the MC4R p.Ile269Asn mutation and BMI in NGT children and adults (children: beta = 3.731 ± 0.958, p = 0.0001; adults: beta = 2.269 ± 0.536, p = 2.3 × 10–5). In contrast, the mutation was not associated with T2D-related quantitative traits. We demonstrate that the MC4R p.Ile269Asn mutation predisposes to T2D via obesity-dependent and independent effects in the Mexican population.Miguel Vázquez-MorenoDaniel Locia-MoralesAdan Valladares-SalgadoTanmay SharmaAleyda Perez-HerreraRoxana Gonzalez-DzibFrancisco Rodríguez-RuízNiels Wacher-RodarteMiguel CruzDavid MeyreNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Miguel Vázquez-Moreno Daniel Locia-Morales Adan Valladares-Salgado Tanmay Sharma Aleyda Perez-Herrera Roxana Gonzalez-Dzib Francisco Rodríguez-Ruíz Niels Wacher-Rodarte Miguel Cruz David Meyre The MC4R p.Ile269Asn mutation confers a high risk for type 2 diabetes in the Mexican population via obesity dependent and independent effects
description	Abstract We investigated the association between the loss-of-function mutation MC4R p.Ile269Asn and T2D risk in the Mexican population. We enrolled 6929 adults [3175 T2D cases and 3754 normal glucose tolerant (NGT) controls] and 994 NGT children in the study. Anthropometric data and T2D-related quantitative traits were studied in 994 NGT children and 3754 NGT adults. The MC4R p.Ile269Asn mutation was genotyped using TaqMan. The MC4R p.Ile269Asn mutation was associated with T2D [OR = 2.00, 95% confidence interval (CI) 1.35–2.97, p = 0.00057] in Mexican adults. Additional adjustment for body-mass index (BMI) attenuated but did not remove the association (OR = 1.70, 95% CI 1.13–2.56, p = 0.011). The MC4R p.Ile269Asn mutation was associated with T2D (OR = 1.88, 95% CI 1.14–3.08, p = 0.013) in a subset of 1269 T2D cases and 1269 NGT controls matched for sex, age, and BMI. A mediation analysis estimated that BMI accounts for 22.7% of the association between MC4R p.Ile269Asn mutation and T2D risk (p = 4.55 × 10–6). An association was observed between the MC4R p.Ile269Asn mutation and BMI in NGT children and adults (children: beta = 3.731 ± 0.958, p = 0.0001; adults: beta = 2.269 ± 0.536, p = 2.3 × 10–5). In contrast, the mutation was not associated with T2D-related quantitative traits. We demonstrate that the MC4R p.Ile269Asn mutation predisposes to T2D via obesity-dependent and independent effects in the Mexican population.
format	article
author	Miguel Vázquez-Moreno Daniel Locia-Morales Adan Valladares-Salgado Tanmay Sharma Aleyda Perez-Herrera Roxana Gonzalez-Dzib Francisco Rodríguez-Ruíz Niels Wacher-Rodarte Miguel Cruz David Meyre
author_facet	Miguel Vázquez-Moreno Daniel Locia-Morales Adan Valladares-Salgado Tanmay Sharma Aleyda Perez-Herrera Roxana Gonzalez-Dzib Francisco Rodríguez-Ruíz Niels Wacher-Rodarte Miguel Cruz David Meyre
author_sort	Miguel Vázquez-Moreno
title	The MC4R p.Ile269Asn mutation confers a high risk for type 2 diabetes in the Mexican population via obesity dependent and independent effects
title_short	The MC4R p.Ile269Asn mutation confers a high risk for type 2 diabetes in the Mexican population via obesity dependent and independent effects
title_full	The MC4R p.Ile269Asn mutation confers a high risk for type 2 diabetes in the Mexican population via obesity dependent and independent effects
title_fullStr	The MC4R p.Ile269Asn mutation confers a high risk for type 2 diabetes in the Mexican population via obesity dependent and independent effects
title_full_unstemmed	The MC4R p.Ile269Asn mutation confers a high risk for type 2 diabetes in the Mexican population via obesity dependent and independent effects
title_sort	mc4r p.ile269asn mutation confers a high risk for type 2 diabetes in the mexican population via obesity dependent and independent effects
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/1876f4c9831d41798d9cb65071b717a1
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The MC4R p.Ile269Asn mutation confers a high risk for type 2 diabetes in the Mexican population via obesity dependent and independent effects

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