Gene–diet interaction between CETP rs3764261 and vegetarian diet on HDL-C levels: evidence for precision nutrition from the Taiwan Biobank

Association Between Prudent Dietary Pattern and Cardiometabolic Indicators in a Healthy Qatari Population: Evidence from the Qatar Biobank (QBB)

Background/Objectives: Diet is recognized as an important determinant of cardiometabolic health, yet evidence from Middle Eastern populations remains scarce. This cross-sectional study investigated the association between a Prudent dietary pattern and multiple indicators of obesity, type-2 diabetes, and cardiovascular disease in a metabolically healthy Qatari cohort. Methods: Data were obtained from 6919 Qatari adults from the Qatar Biobank study. Participants with diagnosed metabolic disorders, pregnancy, or non-fasting blood samples were excluded. Anthropometric, biochemical, and clinical measurements were collected using standardized protocols. Dietary intake was assessed using a 102-item food frequency questionnaire, and a Prudent dietary pattern was derived through factor loadings analysis. Participants were categorized into low and high intake groups of the Prudent dietary pattern. Associations between the Prudent dietary pattern and cardiometabolic markers were examined using generalized linear models adjusted for age, sex, adiposity, and physical activity with Bonferroni correction applied for multiple testing. Results: After correction for multiple testing, greater adherence to the Prudent dietary pattern was significantly associated with lower fat mass index (β = −0.02, p = 0.0001), fasting insulin (β = −0.05, p = 0.0021), and higher fat-free mass (β = 0.01, p = 5.7 × 10−5). Conclusions: Overall, in a metabolically healthy Qatari population, greater compliance to a Prudent dietary pattern was favorably associated with fat and muscle mass, and insulin regulation after adjusting for age, sex, BMI and physical activity. These findings support the role of dietary habits in greater cardiometabolic health in Middle Eastern Arab populations.

Sex-Specific Associations Between MTHFR, PPARG and ADRB3 Polymorphisms, Habitual Nutrient Intake and Metabolic Risk in Obesity: A Cross-Sectional Single-Centre Study

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 ≥ 30 kg/m2; age 18–60 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–Wallis and Mann–Whitney tests with Bonferroni correction (threshold p < 0.017), as well as odds ratios (OR) with 95% confidence intervals. Genotype distributions were tested for Hardy–Weinberg equilibrium, and genotype–nutrient associations were additionally examined in models adjusted for age, BMI and total energy intake. Results: Three genotype–phenotype associations remained significant after Bonferroni correction. In men, the dominant-heterozygous MTHFR C/T genotype was associated with a hypercaloric dietary pattern—excess protein, fat, sodium and phosphorus—and with a high risk of arterial hypertension (OR 5.96, 95% CI 1.48–24.08; 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 1.07–6.43; 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.

The role of genetic variation in apolipoprotein response to diet among Brazilians with cardiovascular disease.

FTO rs9939609 genotype and behavioral determinants of Mediterranean diet adherence in young women: exploratory insights into potential metabolic relevance

Introduction Metabolic disorders such as obesity and insulin resistance result from complex interactions between genetic, behavioral, and dietary factors. The fat mass and obesity-associated (FTO) gene has been repeatedly linked to impaired appetite control and higher obesity risk, yet the moderating role of functional dietary patterns such as the Mediterranean diet remain unclear. Rich in bioactive compounds and metabolic benefits, this diet offers a model for studying gene–diet interactions in metabolic health. Objectives This pilot investigation aimed to provide an integrative perspective linking the FTO rs9939609 genotype with eating-related emotions, habitual behavior, and adherence to a Mediterranean-style diet in women with different body weight profiles. Methods This pilot study examined associations between the FTO rs9939609 genotype, eating behaviors, and adherence to the Mediterranean diet among 46 women aged 18–35 years (normal weight: n = 24; overweight or obesity: n = 22). Eating behaviors were assessed with the Questionnaire of Eating-Related Behaviors (QERB), and diet quality was evaluated using the Mediterranean Pyramid (MedPyr) index. Genotyping was performed by Sanger sequencing. Results Women with overweight or obesity showed higher BMI (p < 0.001) and greater habitual overeating (p = 0.007), particularly among FTO AT/AA carriers with overweight or obesity. Total QERB scores were higher in both TT (p = 0.037) and AT/AA (p = 0.005) subgroups. No significant genotype- or BMI-related differences were observed in overall MedPyr adherence. However, AT/AA carriers with overweight or obesity reported more frequent vegetable intake (p = 0.037), while AT/AA controls consumed eggs more often (p = 0.015). Conclusion Adherence to the Mediterranean diet, a functional dietary pattern rich in polyphenols, fiber, and unsaturated fats, may interact with genetic predispositions related to obesity risk. These exploratory findings suggest that dietary context may shape behavioral tendencies in FTO risk-allele carriers, although confirmation in larger samples is required.

Context-Dependent Associations of the APOA1 rs670 Polymorphism with Apolipoprotein A1 and HDL Cholesterol: A Systematic Review and Meta-Analysis

The APOA1 rs670 (−75 G>A) polymorphism has been implicated in lipid metabolism and susceptibility to metabolic syndrome (MetS). However, individual studies have reported inconsistent associations with circulating apolipoprotein A1 (Apo A1) and lipid parameters, and no meta-analysis has comprehensively evaluated these associations stratified by metabolic disorder status. We therefore quantified the associations between APOA1 rs670 and serum Apo A1 and lipid parameters, and determined whether these associations are modified by metabolic disorder status. PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov were searched from inception to March 2026. Eligible studies reported APOA1 rs670 genotype data with quantitative lipid measurements. Forty studies involving 22,175 participants met the inclusion criteria. Pooled effect sizes were estimated as standardized mean differences (SMDs) with 95% confidence intervals (CIs) using random-effects models. This review was registered in PROSPERO (CRD420261333145). A allele carriers had significantly higher serum Apo A1 (SMD, 0.20; p < 0.001) and HDL-C levels (SMD, 0.14; p < 0.001) than GG homozygotes. Subgroup analyses stratified by metabolic disorder status revealed that the associations with Apo A1 (SMD, 0.53 vs. 0.11) and HDL-C (SMD, 0.23 vs. 0.08) were substantially stronger among individuals with metabolic disorders than among metabolically healthy individuals. No significant associations were observed for LDL-C or triglyceride levels. The APOA1 rs670 polymorphism is associated with higher circulating Apo A1 and HDL-C levels, with stronger associations in individuals with metabolic disorders. These findings suggest that metabolic status modifies the phenotypic effects of rs670 on the Apo A1–HDL pathway.

Coffee Intake is Associated with Improved Insulin Sensitivity and Lower Visceral Adiposity: Evidence from Biomarker and Genetic Analysis