{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T15:41:31Z","timestamp":1782142891794,"version":"3.54.5"},"reference-count":48,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CONACyT-PEI","award":["230129"],"award-info":[{"award-number":["230129"]}]},{"name":"CONACyT-PEI","award":["289699"],"award-info":[{"award-number":["289699"]}]},{"name":"CONACyT-PEI","award":["777140"],"award-info":[{"award-number":["777140"]}]},{"name":"CONACyT-FOSISS","award":["230129"],"award-info":[{"award-number":["230129"]}]},{"name":"CONACyT-FOSISS","award":["289699"],"award-info":[{"award-number":["289699"]}]},{"name":"CONACyT-FOSISS","award":["777140"],"award-info":[{"award-number":["777140"]}]},{"name":"CONACyT scholarship","award":["230129"],"award-info":[{"award-number":["230129"]}]},{"name":"CONACyT scholarship","award":["289699"],"award-info":[{"award-number":["289699"]}]},{"name":"CONACyT scholarship","award":["777140"],"award-info":[{"award-number":["777140"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>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\u20139.7), 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: \u22124.0 kg (\u22122.9%) in patient 1, and \u22121.8 kg (\u22121.5%) in patient 2; similar to the mean weight loss observed in six non-carrier subjects (\u22122.9 kg; \u22122.8%). Phentermine treatment produced similar weight loss in six carriers (\u221212.7 kg; 15.5%) and 18 non-carriers (\u221211.3 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.<\/jats:p>","DOI":"10.3390\/genes13122267","type":"journal-article","created":{"date-parts":[[2022,12,2]],"date-time":"2022-12-02T02:18:06Z","timestamp":1669947486000},"page":"2267","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Effect of the Melanocortin 4-Receptor Ile269Asn Mutation on Weight Loss Response to Dietary, Phentermine and Bariatric Surgery Interventions"],"prefix":"10.3390","volume":"13","author":[{"given":"Itzel G.","family":"Salazar-Valencia","sequence":"first","affiliation":[{"name":"Unidad de Gen\u00f3mica de Poblaciones Aplicada a la Salud, Facultad de Qu\u00edmica, Universidad Nacional Aut\u00f3noma de M\u00e9xico (UNAM), Mexico City 14610, Mexico"},{"name":"Instituto Nacional de Medicina Gen\u00f3mica (INMEGEN), Mexico City 14610, Mexico"},{"name":"Programa de Maestr\u00eda en Ciencias Bioqu\u00edmicas, Facultad de Qu\u00edmica, Universidad Nacional Aut\u00f3noma de M\u00e9xico (UNAM), Mexico City 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugo","family":"Villamil-Ram\u00edrez","sequence":"additional","affiliation":[{"name":"Unidad de Gen\u00f3mica de Poblaciones Aplicada a la Salud, Facultad de Qu\u00edmica, Universidad Nacional Aut\u00f3noma de M\u00e9xico (UNAM), Mexico City 14610, Mexico"},{"name":"Instituto Nacional de Medicina Gen\u00f3mica (INMEGEN), Mexico City 14610, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5064-6203","authenticated-orcid":false,"given":"Francisco","family":"Barajas-Olmos","sequence":"additional","affiliation":[{"name":"Laboratorio de Immunogen\u00f3mica y Enfermedades Metab\u00f3licas, Instituto Nacional de Medicina Gen\u00f3mica (INMEGEN), Mexico City 14610, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8996-3481","authenticated-orcid":false,"given":"Martha","family":"Guevara-Cruz","sequence":"additional","affiliation":[{"name":"Departmento de Fisiolog\u00eda de la Nutrici\u00f3n, Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n Salvador Zubir\u00e1n, Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3080-2835","authenticated-orcid":false,"given":"Luis R.","family":"Macias-Kauffer","sequence":"additional","affiliation":[{"name":"Unidad de Gen\u00f3mica de Poblaciones Aplicada a la Salud, Facultad de Qu\u00edmica, Universidad Nacional Aut\u00f3noma de M\u00e9xico (UNAM), Mexico City 14610, Mexico"},{"name":"Instituto Nacional de Medicina Gen\u00f3mica (INMEGEN), Mexico City 14610, 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Poblaciones Aplicada a la Salud, Facultad de Qu\u00edmica, Universidad Nacional Aut\u00f3noma de M\u00e9xico (UNAM), Mexico City 14610, Mexico"},{"name":"Instituto Nacional de Medicina Gen\u00f3mica (INMEGEN), Mexico City 14610, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Le\u00f3n-Mimila","sequence":"additional","affiliation":[{"name":"Unidad de Gen\u00f3mica de Poblaciones Aplicada a la Salud, Facultad de Qu\u00edmica, Universidad Nacional Aut\u00f3noma de M\u00e9xico (UNAM), Mexico City 14610, Mexico"},{"name":"Instituto Nacional de Medicina Gen\u00f3mica (INMEGEN), Mexico City 14610, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3512-4519","authenticated-orcid":false,"given":"Federico","family":"Centeno-Cruz","sequence":"additional","affiliation":[{"name":"Laboratorio de Immunogen\u00f3mica y Enfermedades Metab\u00f3licas, Instituto Nacional de Medicina Gen\u00f3mica (INMEGEN), 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Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1172\/JCI9397","article-title":"Dominant and recessive inheritance of morbid obesity associated with melanocortin 4 receptor deficiency","volume":"2","author":"Farooqi","year":"2000","journal-title":"J. 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