{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T08:45:57Z","timestamp":1785833157717,"version":"3.56.0"},"reference-count":37,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Federal Research Centre of Nutrition, Biotechnology and Food Safety","award":["FGMF-2026-0014"],"award-info":[{"award-number":["FGMF-2026-0014"]}]},{"award":["FGMF-2026-0014"],"award-info":[{"award-number":["FGMF-2026-0014"]}],"id":[{"id":"https:\/\/ror.org\/05ssfag15","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Genetic polymorphisms modulate the risk of metabolic complications of obesity; yet, it remains unclear how genotype reshapes actual dietary intake and why these mechanisms differ between men and women. The aim of this study was to identify sex-specific associations of three common polymorphisms (MTHFR C677T, PPARG Pro12Ala, ADRB3 Trp64Arg) with habitual nutrient intake in patients with obesity, and to explore candidate sex-differentiated dietary hypotheses for future prospective testing. Methods: A single-centre cross-sectional study was performed in 348 patients with obesity (83 men, 265 women; BMI \u2265 30 kg\/m2; age 18\u201360 years). Genotyping was performed by allele-specific real-time PCR from buccal swabs. Habitual intake of more than 18 nutrients was assessed using a standardised Russian software-based questionnaire. Statistical analysis included Kruskal\u2013Wallis and Mann\u2013Whitney tests with Bonferroni correction (threshold p &lt; 0.017), as well as odds ratios (OR) with 95% confidence intervals. Genotype distributions were tested for Hardy\u2013Weinberg equilibrium, and genotype\u2013nutrient associations were additionally examined in models adjusted for age, BMI and total energy intake. Results: Three genotype\u2013phenotype associations remained significant after Bonferroni correction. In men, the dominant-heterozygous MTHFR C\/T genotype was associated with a hypercaloric dietary pattern\u2014excess protein, fat, sodium and phosphorus\u2014and with a high risk of arterial hypertension (OR 5.96, 95% CI 1.48\u201324.08; p = 0.010). The sodium load in C\/T carriers was a consequence of overall overeating rather than a selective preference for salty foods. In men, ADRB3 Trp64Arg carriage was associated with massive dietary cholesterol overconsumption (+466% vs. +153% in Trp\/Trp; p = 0.012), whereas in women the opposite direction was observed. The PPARG G\/G genotype in women was associated with elevated alanine aminotransferase (p = 0.027), most pronounced under 40 years (p = 0.011), and is considered a marker of hepatic risk without a confirmed dietary target. In women, the MTHFR T\/T homozygous genotype showed suggestive associations with excessive mono-\/disaccharide intake and a tendency toward hypertension (OR 2.62, 95% CI 1.07\u20136.43; p = 0.035); however, these did not survive FDR correction and require independent validation. Conclusions: Genetic polymorphisms were associated with sex-specific patterns of actual dietary intake, a finding that extends current knowledge beyond biochemical risk associations. Based on these associations, we propose testable hypotheses rather than clinical recommendations: that caloric restriction (with consequent sodium reduction) in men with MTHFR C\/T, cholesterol restriction in men with ADRB3 Arg64, and mono-\/disaccharide restriction in women with MTHFR T\/T might reduce metabolic risk; women with PPARG G\/G may warrant ALT monitoring. These findings suggest that genotype-informed dietary strategies may need to be sex-specific, and that the window for intervention may be earlier in life than currently practised. However, these hypotheses require prospective interventional validation before any clinical application.<\/jats:p>","DOI":"10.3390\/nu18152522","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T08:02:19Z","timestamp":1785830539000},"page":"2522","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sex-Specific Associations Between MTHFR, PPARG and ADRB3 Polymorphisms, Habitual Nutrient Intake and Metabolic Risk in Obesity: A Cross-Sectional Single-Centre Study"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0963-0792","authenticated-orcid":false,"given":"Irina A.","family":"Lapik","sequence":"first","affiliation":[{"name":"Federal Research Centre of Nutrition, Biotechnology and Food Safety, 2\/14 Ustinsky Proyezd, Moscow 109240, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7791-1222","authenticated-orcid":false,"given":"Inna Yu.","family":"Tarmaeva","sequence":"additional","affiliation":[{"name":"Federal Research Centre of Nutrition, Biotechnology and Food Safety, 2\/14 Ustinsky Proyezd, Moscow 109240, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4968-4517","authenticated-orcid":false,"given":"Dmitry B.","family":"Nikityuk","sequence":"additional","affiliation":[{"name":"Federal Research Centre of Nutrition, Biotechnology and Food Safety, 2\/14 Ustinsky Proyezd, Moscow 109240, Russia"},{"name":"I.M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of the Russian Federation, Moscow 119991, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,4]]},"reference":[{"key":"ref_1","unstructured":"GBD 2021 Adult BMI Collaborators (2025). Global, regional, and national prevalence of adult overweight and obesity, 1990\u20132021, with forecasts to 2050: A forecasting study for the Global Burden of Disease Study 2021. Lancet, 405, 813\u2013838."},{"key":"ref_2","first-page":"6","article-title":"Key problems in the structure of food consumption and breakthrough technologies for nutrition optimization for health preservation of the Russian population","volume":"93","author":"Tutelyan","year":"2024","journal-title":"Probl. 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