MTNR1B genotype and effects of carbohydrate quantity and dietary glycaemic index on glycaemic response to an oral glucose load: the OmniCarb trial.

AIMS/HYPOTHESIS: A type 2 diabetes-risk-increasing variant, MTNR1B (melatonin receptor 1B) rs10830963, regulates the circadian function and may influence the variability in metabolic responses to dietary carbohydrates. We investigated whether the effects of carbohydrate quantity and dietary glycaemic index (GI) on glycaemic response during OGTTs varied by the risk G allele of MTNR1B-rs10830963. METHODS: This study included participants (n=150) of a randomised crossover-controlled feeding trial of four diets with high/low GI levels and high/low carbohydrate content for 5 weeks. The MTNR1B-rs10830963 (C/G) variant was genotyped. Glucose response during 2 h OGTT was measured at baseline and the end of each diet intervention. RESULTS: Among the four study diets, carrying the risk G allele (CG/GG vs CC genotype) of MTNR1B-rs10830963 was associated with the largest AUC of glucose during 2 h OGTT after consuming a high-carbohydrate/high-GI diet (ß 134.32 [SE 45.69] mmol/l × min; p=0.004). The risk G-allele carriers showed greater increment of glucose during 0-60 min (ß 1.26 [0.47] mmol/l; p=0.008) or 0-90 min (ß 1.10 [0.50] mmol/l; p=0.028) after the high-carbohydrate/high-GI diet intervention, but not after consuming the other three diets. At high carbohydrate content, reducing GI levels decreased 60 min post-OGTT glucose (mean -0.67 [95% CI: -1.18, -0.17] mmol/l) and the increment of glucose during 0-60 min (mean -1.00 [95% CI: -1.67, -0.33] mmol/l) and 0-90 min, particularly in the risk G-allele carriers (pinteraction <0.05 for all). CONCLUSIONS/INTERPRETATION: Our study shows that carrying the risk G allele of MTNR1B-rs10830963 is associated with greater glycaemic responses after consuming a diet with high carbohydrates and high GI levels. Reducing GI in a high-carbohydrate diet may decrease post-OGTT glucose concentrations among the risk G-allele carriers.

Interplay of Mediterranean-diet adherence, genetic factors, and metabolic dysfunction-associated steatotic liver disease risk in Korea.

BACKGROUNDS: Metabolic dysfunction-associated steatotic liver disease (MASLD) has gained attention owing to its severe complications. This study aimed to explore the interaction between Mediterranean-diet (MD) adherence, genetic factors, and MASLD risk in a Korean population. METHODS: In total, 33,133 individuals aged 40 years and older from the Korean Genome and Epidemiology Study (KoGES) were analyzed. Participants were assessed for MASLD based on criteria and MD adherence measured by the Korean version of the Mediterranean-Diet Adherence Screener (K-MEDAS). Individuals were categorized into two groups based on their MD adherence: high adherence (K-MEDAS > 6) and low adherence (K-MEDAS < 5). Single nucleotide polymorphism (SNP) genotypes were obtained using the Korea Biobank array. Logistic regression was used to examine the single-marker variants for genetic associations with MASLD prevalence. RESULTS: Individuals were categorized into MASLD (10,018 [30.2%]) and non-MASLD (23,115 [69.8%]) groups. A significant interaction was observed between the rs780094 glucokinase regulatory protein (GCKR) gene and K-MEDAS on MASLD (p < 10 - 2 ). Of individuals with K-MEDAS > 6, those carrying the minor allele (C) of the GCKR gene rs780094 exhibited a lower risk of MASLD compared to those without the allele (odds ratio [OR] = 0.88 [0.85-0.91], p-value = 5.54e-13). CONCLUSION: The study identified a significant interaction involving the rs780094 variant near the GCKR gene, with carriers of the minor allele exhibiting a lower MASLD risk among those adhering well to the MD. Dietary habits influence the MASLD risk associated with the rs780094 allele, emphasizing the need for personalized nutrition recommendations.

Evidence of gene-nutrient interaction association with waist circumference, cross-sectional analysis.

BACKGROUND AND AIMS: Waist circumference (WC) is a significant indicator of body adiposity and is associated with increased mortality and morbidity of cardiovascular diseases. Although, single nutrient intake and candidate genes were previously associated with WC. Little is known about WC association with overall diet quality, genetic risk score and gene-nutrient interaction. This study aims to investigate the influence of overall diet quality and multiple WC-associated single nucleotide polymorphisms on WC. In addition to investigating gene-nutrient interaction association with WC. METHODS: This study explored cross-sectional data from two large sample-size studies, to provide reproducible results. As a representation of the UK population, the Airwave Health Monitoring Study (n = 6,502) and the UK-Biobank Cohort Study (n = 171,129) were explored for factors associated with WC. Diet quality was evaluated based on the Mellen Index for Dietary Approaches to Stop Hypertension (Mellen-DASH). The genetic risk score for WC (GRS-Waist) was calculated by screening the population genotype for WC-associated single nucleotide polymorphisms. Multivariate linear regression models were built to explore WC association with diet quality and genetic risk score. Gene-nutrient interaction was explored by introducing the interaction term (GRS-Waist X Mellen-DASH score) to multivariate linear regression analysis. RESULTS: The prevalence of high WC (Female > 80 cm, Male > 94 cm) was 46.5% and 51.7% in both populations. Diet quality and genetic risk score of WC were significantly associated with WC. There was no evidence of interaction between GRS-Waist, DASH diet scores and nutrient intake on WC. CONCLUSION: This study's findings provided reproducible results on waist circumference association with diet and genetics and tested the possibility of gene-nutrient interaction. These reproducible results are successful in building the foundation for using diet and genetics for early identification of those at risk of having high WC and WC-associated diseases. In addition, evidence on gene-diet interactions on WC is limited and lacks replication, therefore our findings may guide future research in investigating this interaction and investigating its application in precision nutrition.

Dietary Sources, Sex, and rs5888 (SCARB1) as Modulators of Vitamin A's Effect on Cardiometabolic Health.

Although preclinical studies have attributed vitamin A (VA) cardiometabolic benefits, these effects are still controversial and not always supported in large human studies. Here, the outcomes associated with VA and its relationship with habitual dietary sources, sex, and genetic background have been studied. To do so, the data from an observational study (n = 455) (64% females, mean age of 36 years) showing that suboptimal VA intake (mainly from retinol rather than carotene) is associated with cardiometabolic risk (CMR) were considered. A higher odds ratio (OR) of suffering ≥ 2 simultaneous CMR factors was observed in men in the low consumption tercile of retinol (OR = 2.04; p = 0.019). In women, however, this relationship was not evident. Then, incubation of peripheral blood mononuclear cells (PBMCs) with VA-related compounds (ex vivo functional assay from 81 men and women) induced specific changes in the activity of genes involved in lipid homeostasis and inflammatory status, which were dependent on the type of compound tested and the sex of the person. In addition, the presence of the genetic variant rs5888 in SCARB1 was identified as having a high influence on VA-related metabolic response. The new evidence derived from this study could be relevant for personalized nutritional advice concerning VA and CMR.

Chrono-Nutrition: Circadian Rhythm and Personalized Nutrition.

The human circadian system has a period of approximately 24 h and studies on the consequences of "chornodisruption" have greatly expanded. Lifestyle and environmental factors of modern societies (i.e., artificial lighting, jetlag, shift work, and around-the-clock access to energy-dense food) can induce disruptions of the circadian system and thereby adversely affect individual health. Growing evidence demonstrates a complex reciprocal relationship between metabolism and the circadian system, in which perturbations in one system affect the other one. From a nutritional genomics perspective, genetic variants in clock genes can both influence metabolic health and modify the individual response to diet. Moreover, an interplay between the circadian rhythm, gut microbiome, and epigenome has been demonstrated, with the diet in turn able to modulate this complex link suggesting a remarkable plasticity of the underlying mechanisms. In this view, the study of the impact of the timing of eating by matching elements from nutritional research with chrono-biology, that is, chrono-nutrition, could have significant implications for personalized nutrition in terms of reducing the prevalence and burden of chronic diseases. This review provides an overview of the current evidence on the interactions between the circadian system and nutrition, highlighting how this link could in turn influence the epigenome and microbiome. In addition, possible nutritional strategies to manage circadian-aligned feeding are suggested.

Interactions between Bitter Taste Receptor Gene Variants and Dietary Intake Are Associated with the Incidence of Type 2 Diabetes Mellitus in Middle-Aged and Older Korean Adults.

The relationship between the variants of bitter taste receptor gene TAS2R4, dietary intake, and incidence of type 2 diabetes mellitus (T2DM) remains unclear. Hence, we aimed to examine the association of TAS2R4 rs2233998 variants with T2DM incidence in middle-aged and older Korean adults to understand if their association was modulated by dietary intake. Data of the Ansan-Ansung cohort from the Korean Genome and Epidemiology Study were used in this study. A total of 4552 Korean adults aged 40-69 years with no history of T2DM or cancer at baseline were followed-up for 16 years. Dietary intake was assessed using a 103-item food frequency questionnaire, and new T2DM cases were defined based on the World Health Organization and International Diabetes Federation criteria. Multivariate Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for T2DM incidence. During the mean follow-up period of 11.97 years, 1082 (23.77%) new T2DM cases were identified. Women carrying the TT genotype of TAS2R4 rs2233998 exhibited 1.48 times higher incidence of T2DM (HR: 1.48; 95 CI: 1.13-1.93) than those carrying the CC genotype. TAS2R4 rs2233998 variants were positively associated with the incidence of T2DM among Korean women with high intakes of carbohydrates or sugars and low intakes of fruits or vegetables. TT carrier women in the highest tertile of carbohydrate or sugar intake exhibited an increased incidence of T2DM (HR: 2.08, 95% CI: 1.33-3.27 for carbohydrates; HR: 2.31, 95% CI: 1.53-3.51 for sugars) than CC carrier women. Women carrying the TT genotype in the lowest tertile exhibited an increased incidence of T2DM (HR: 1.55, 95% CI: 1.02-2.37 for vegetables; HR: 1.62, 95% CI: 1.06-2.48 for fruits) than women carrying the CC genotype in the highest tertile of vegetable or fruit consumption. However, no association was observed between TAS2R4 rs2233998 variants and dietary intake with T2DM incidence in Korean men. Our findings suggest that variants of TAS2R4 rs2233998 are associated with T2DM incidence, and their associations are strengthened by excessive intake of carbohydrates or sugars and inadequate intake of fruits or vegetables. Diet encompassing optimal intake of carbohydrates or sugars and high intake of fruits or vegetables may minimize the risk of developing T2DM.

In the context of the triple burden of malnutrition: A systematic review of gene-diet interactions and nutritional status.

Genetic background interacts with dietary components to modulate nutritional health status. This study aimed to review the evidence for gene-diet interactions in all forms of malnutrition. A comprehensive systematic literature search was conducted through April 2021 to identify observational and intervention studies reporting the effects of gene-diet interactions in over-nutrition, under-nutrition and micronutrient status. Risk of publication bias was assessed using the Quality Criteria Checklist and a tool specifically designed for gene-diet interaction research. 167 studies from 27 populations were included. The majority of studies investigated single nucleotide polymorphisms (SNPs) in overnutrition (n = 158). Diets rich in whole grains, vegetables, fruits and low in total and saturated fats, such as Mediterranean and DASH diets, showed promising effects for reducing obesity risk among individuals who had higher genetic risk scores for obesity, particularly the risk alleles carriers of FTO rs9939609, rs1121980 and rs1421085. Other SNPs in MC4R, PPARG and APOA5 genes were also commonly studied for interaction with diet on overnutrition though findings were inconclusive. Only limited data were found related to undernutrition (n = 1) and micronutrient status (n = 9). The findings on gene-diet interactions in this review highlight the importance of personalized nutrition, and more research on undernutrition and micronutrient status is warranted.

Caveolin-1 genetic polymorphism interacts with PUFA to modulate metabolic syndrome risk.

Several studies have reported a significant association between the metabolic syndrome (MetS) and mortality around the world. Caveolin-1 (CAV-1) has been widely studied in dyslipidaemia, and several studies have indicated that CAV-1 genetic variations may correlate with dietary intake of fatty acids. This study aimed to investigate the interaction of CAV-1 rs3807992 with types of dietary fatty acid in the MetS risk. This cross-sectional study was carried out on 404 overweight and obese females. Dietary intake was obtained from a 147-item FFQ. The CAV-1 genotype was measured using the PCR-restriction fragment length polymorphism method. Anthropometric values and serum levels (TC, LDL, HDL, TAG and FBS) were measured by standard methods. It was observed that the (AA + AG) group had significantly higher BMI, waist circumference and DBP (P = 0·02, P = 0·02, and P = 0·01, respectively) and lower serum LDL, HDL and TC (P < 0·05) than the GG group. It was found that A allele carriers were at higher odds of the MetS (P = 0·01), abdominal obesity (P = 0·06), increased TAG concentration (P = 0·01), elevated blood pressure (BP) (P = 0·01), increased glucose concentration (P = 0·45) and decreased HDL-cholesterol concentration (P = 0·03). Moreover, the interaction of CAV-1 and SFA intake was significant in terms of the MetS (P = 0·03), LDL (P = 0·03) and BP (P = 0·01). Additionally, the (AA + AG) group was significantly related to PUFA intake in terms of the MetS (P = 0·04), TAG (P = 0·02), glucose (P = 0·02) and homoeostasis model assessment insulin resistance (P = 0·01). Higher PUFA consumption might attenuate the CAV-1 rs3807992 associations with the MetS, and individuals with greater genetic predisposition appeared to have a higher risk of the MetS, associated with higher SFA consumption.

Interaction of MC4R rs17782313 variants and dietary carbohydrate quantity and quality on basal metabolic rate and general and central obesity in overweight/obese women: a cross-sectional study.

BACKGROUND: Recent studies have shown that dietary carbohydrate quantity and quality as well as genetic variants may contribute to determining the metabolic rate and general and central obesity. This study aimed to examine interactions between melanocortin 4 receptor gene (MC4R) rs17782313 and dietary carbohydrate intake, glycemic index (GI), and glycemic load (GL) on body mass index (BMI), waist circumferences (WC), basal metabolic rate (BMR), and BMR/kg in overweight/obese women. METHODS: A total of 282 Iranian women (BMI ≥ 25) aged 18-56 years were enrolled in this cross-sectional study. All participants were assessed for blood parameters, body composition, BMR, and dietary intake. Dietary carbohydrate intake, GI, and GL were determined using a valid, reliable 147-item food frequency questionnaire. MC4R rs17782313 was genotyped by the restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: After adjustment for age and energy intake, significant interactions were observed between carbohydrate intake and MC4R rs17782313 in terms of BMI (P Interaction = 0.007), WC (P Interaction = 0.02), and BMR/kg (P Interaction = 0.003) in this way that higher carbohydrate intake, compared with lower intake, was associated with an increase in BMI and WC for individuals with C allele carriers (TC + CC genotypes), while related to an increase in BMR/kg for those carrying the TT genotype. No significant interaction was found between MC4R rs17782313 and GI and GL on BMI, WC, BMR/kg, and BMR. CONCLUSIONS: Interactions between the MC4R rs17782313 and carbohydrate intake probably can have an effect on BMI, WC, and BMR/kg in overweight/obese women.

Interplay between fatty acid desaturase2 (FADS2) rs174583 genetic variant and dietary antioxidant capacity: cardio-metabolic risk factors in obese individuals.

OBJECTIVE: Polymorphisms of the fatty acid desaturase (FADS) gene cluster have been associated with obesity and its-related consequences. This cross-sectional study aimed to investigate whether the adherence to dietary non-enzymatic antioxidant capacity (NEAC), reflecting the antioxidant potential of the whole diet, modifies the association of FADS2 rs174583 polymorphism with cardio-metabolic risk factors in obese adults. METHODS: The present study included 347 healthy obese adults (aged 20-50 years). Dietary NEAC was assessed by a validated food frequency questionnaire with 147 items and estimated through total radical-trapping antioxidant parameters (TRAP), oxygen radical absorbance capacity (ORAC), and ferric reducing ability of plasma (FRAP) with the use of published databases. FADS2 rs174583 polymorphism was characterized using PCR-RFLP. ANCOVA multivariate interaction model was used to analyze gene-diet interactions. RESULTS: after adjustment for the confounding variables (age, physical activity, SES and WC), this study showed significant interactions between rs174583 polymorphism and adherence to dietary ORAC on the serum cholesterol (P Interaction = 0.029), LDL-C (P Interaction = 0.025) and HDL-C levels (P Interaction = 0.049) among the male group; minor allele carriers who had the highest adherence to the NEAC (ORAC) showed a better metabolic profile (lower TG and LDL-C and higher HDL-C) (P < 0.05). Among women, the dietary ORAC-rs174583 interactions were statistically significant for the serum insulin concentration (P Interaction = 0.020), QUICKI (P Interaction = 0.023) and HOMA-IR (P Interaction = 0.017); the highest QUICKI and the lowest HOMA-IR and serum insulin levels were observed in the CC homozygote carriers with the moderate compliance with the dietary ORAC (P < 0.05). In addition, the dietary TRAP modified the association between FADS2 variant and change in LDL-C levels (P Interaction = 0.037); the homozygous wild-type (CC) women who placed in the top tertile of TRAP had significantly the lowest LDL-C levels than those in the second tertile (P < 0.05). CONCLUSION: These data indicate that the FADS2 rs174583 polymorphism interacts with the dietary NEAC to influence cardio-metabolic risk factors in obese subjects. Replication in prospective cohort studies among other populations is required to confirm the results of our study.

Gene-diet interactions and cardiovascular diseases: a systematic review of observational and clinical trials.

BACKGROUND: Both genetic background and diet are important determinants of cardiovascular diseases (CVD). Understanding gene-diet interactions could help improve CVD prevention and prognosis. We aimed to summarise the evidence on gene-diet interactions and CVD outcomes systematically. METHODS: We searched MEDLINE® via Ovid, Embase, PubMed®, and The Cochrane Library for relevant studies published until June 6th 2022. We considered for inclusion cross-sectional, case-control, prospective cohort, nested case-control, and case-cohort studies as well as randomised controlled trials that evaluated the interaction between genetic variants and/or genetic risk scores and food or diet intake on the risk of related outcomes, including myocardial infarction, coronary heart disease (CHD), stroke and CVD as a composite outcome. The PROSPERO protocol registration code is CRD42019147031. RESULTS AND DISCUSSION: We included 59 articles based on data from 29 studies; six articles involved multiple studies, and seven did not report details of their source population. The median sample size of the articles was 2562 participants. Of the 59 articles, 21 (35.6%) were qualified as high quality, while the rest were intermediate or poor. Eleven (18.6%) articles adjusted for multiple comparisons, four (7.0%) attempted to replicate the findings, 18 (30.5%) were based on Han-Chinese ethnicity, and 29 (49.2%) did not present Minor Allele Frequency. Fifty different dietary exposures and 52 different genetic factors were investigated, with alcohol intake and ADH1C variants being the most examined. Of 266 investigated diet-gene interaction tests, 50 (18.8%) were statistically significant, including CETP-TaqIB and ADH1C variants, which interacted with alcohol intake on CHD risk. However, interactions effects were significant only in some articles and did not agree on the direction of effects. Moreover, most of the studies that reported significant interactions lacked replication. Overall, the evidence on gene-diet interactions on CVD is limited, and lack correction for multiple testing, replication and sample size consideration.

The interaction between Alternative Healthy Eating Index and MC4R rs17782313 gene variants on central and general obesity indices in women: A cross-sectional study.

BACKGROUND: Previous studies have shown that the C allele of melanocortin 4 receptor (MC4R) rs17782313 and the Alternative Healthy Eating Index (AHEI) are separately associated with obesity. However, the present study aimed to investigate the interaction between MC4R rs17782313 variants and the AHEI and their association with central and general obesity indices, which has not been assessed previously. METHODS: In total, 291 women with body mass index (BMI) ≥ 25 kg m-2 and aged 18-48 years enrolled in this cross-sectional study. All participants were assessed for body composition, anthropometric measures, dietary intake, and blood parameters. After obtaining data of dietary intake from the 147-item food frequency questionnaire, the AHEI was calculated. MC4R rs17782313 single-nucleotide polymorphisms were assessed using the polymerase chain reaction-restriction length polymorphism method. RESULTS: After adjustment for age, energy intake, physical activity, marital status, and economic status, the interaction between MC4R rs17782313 and the AHEI was associated with hip circumference [ß = -0.41, 95% confidence interval (CI) = -0.77 to -0.05, p = 0.02], BMI (ß = -0.15, 95% CI = -0.29 to -0.02, p = 0.02), fat mass (kg) (ß = -0.28, 95% CI = -0.56 to -0.01, p = 0.03), visceral fat area (ß = -5.68, 95% CI = -9.55 to -1.80, p = 0.004). The other measures that appear to be suggestively related to this interaction (0.05 < p < 0.07) are waist circumference, waist-to-height ratio, trunk fat (%), trunk fat (kg), fat mass (%) and fat mass index. CONCLUSIONS: The interaction between MC4R rs17782313 and the AHEI can be related to central and general obesity indices in overweight/obese women.

A personalised diet approach study: Interaction between PPAR-γ Pro12Ala and dietary insulin indices on metabolic markers in diabetic patients.

BACKGROUND: The present study aimed to investigate the effect of the interaction between peroxisome proliferator-activated receptor gamma (PPAR-γ) Pro12Ala polymorphisms and dietary insulin load and insulin index (DIL and DII) on cardio-metabolic markers among diabetic patients. METHODS: This cross-sectional study was conducted on 393 diabetic patients. A food-frequency questionnaire was used for DIL and DII calculation. PPAR-γ Pro12Ala was genotyped by a polymerase chain reaction-restriction fragment length polymorphism method. Biochemical markers, including total cholesterol, low-density lipoprotein, high-density lipoprotein, triglyceride, superoxide dismutase, C-reactive protein, total antioxidant capacity, pentraxin-3, isoprostaneF2α, interleukin-18, leptin and ghrelin, were measured by a standard protocol. RESULTS: Risk-allele carriers (CG, GG) had higher obesity indices [body mass index (pinteraction = 0.006) and WC (pinteraction = 0.04)] compared to individuals with the CC genotype when they consumed a diet with higher DIL and DII respectively. Besides, carriers of the G-allele who were in the highest tertile of DIL had lower high-density lipoprotein (pinteraction = 0.04) and higher isoprostaneF2α (pinteraction = 0.03) and pentraxin-3 (pinteraction = 0.03). Moreover, the highest tertile of the DII, showed an increase in interleukin-18 (pinteraction = 0.01) and lower superoxide dismutase (pinteraction = 0.03) for risk-allele carriers compared to those with CC homozygotes. CONCLUSIONS: We revealed that the PPAR-γ Pro12Ala polymorphism was able to intensify the effect of DIL and DII on cardiovascular disease risk factors; risk-allele carriers who consumed a diet with high DIL and DII score were more likely to be obese and have higher inflammatory markers. Also, protective factors against cardiovascular disease risk factors were reduced significantly in this group compared to CC homozygotes.

Diet Modulates the Effects of Genetic Variants on the Vitamin D Metabolic Pathway and Bone Mineral Density in Mexican Postmenopausal Women.

BACKGROUND: Macro- and micronutrients, such as proteins, vitamin D, and calcium (Ca), are important dietary factors that can modify bone mineral density (BMD). Genetic factors can interact with diet, affecting an individual's predisposition to osteoporosis. OBJECTIVES: This study aimed to evaluate the associations between macro- and micronutrient intakes and BMD in Mexican postmenopausal women, and their interactions with genetic polymorphisms involved in the vitamin D metabolic pathway. METHODS: We analyzed data from 317 postmenopausal women from the Health Workers Cohort Study, a longitudinal cohort studied in Cuernavaca, Mexico. Postmenopausal women participated in 2 data collection waves (2004-2006 and 2010-2011), with a mean time of 6.4 years. Dietary intake was assessed with a semi-quantitative FFQ. BMD (femoral neck, hip, and lumbar spine) was measured by DXA. Hybrid mixed-effects regression models were used to assess the associations of dietary macro- and micronutrients on BMD, after adjusting for confounding factors and for diet and single nucleotide polymorphism interactions. RESULTS: At baseline, the median age was 57 years (IQR, 50-64). Mean femoral neck, hip, and lumbar spine BMDs decreased over time. We observed statistically significant longitudinal associations for diet (Ca, vitamin D, magnesium, phosphorus, and protein intake) and BMD. Increases of vitamin D, Ca, and protein intakes by 1 SD were associated with mean increases in the femoral neck BMD (0.083 SD, 0.064 SD, and 0.130 SD, respectively). Multiple significant interactions were identified between several loci (CYP2R1, CYP24A1, CYP27B1, VDR, and DHCR7/NADSYN1) and diet for BMDs (femoral neck, hip, and lumbar spine), mainly for protein intake. CONCLUSIONS: Our data support associations of vitamin D, Ca, protein, phosphorous, and magnesium consumption with BMD in Mexican postmenopausal women and suggest possible gene-diet interactions. These results could facilitate future personalized nutrition recommendations to help prevent low BMD.

Diet-gene interaction: effects of polymorphisms in the ACE, AGT and BDKRB2 genes and the consumption of sodium, potassium, calcium, and magnesium on blood pressure of normotensive adult individuals.

Functional variants in genes of the renin-angiotensin (RAS) and kallikrein-kinin (KKS) systems have already been implicated in blood pressure (BP) modulation, but few studies have focused on a nutrigenetics approach. Thus, the aim of this study is to verify the effects of the interaction between genetic polymorphisms (rs4340-ACE, rs699-AGT, and rs1799722-BDKRB2) and micronutrient consumption (sodium, potassium, calcium, and magnesium) on BP values of normotensive adult individuals. The study included 335 adults, men and women, 25.5 (6.6) years old. Biochemical, anthropometric, BP measurements, and food intake data were assessed for all participants. Gene-nutrient interaction on BP outcome was tested by multiple linear regression with manual backward stepwise modeling. Our results indicated that individuals with G allele for rs699 polymorphism, in the increase of sodium and magnesium consumption, both in the genotypic model (sodium, p = 0.035; magnesium, p = 0.016) and in the dominant model (sodium, p = 0.009; magnesium, p = 0.006) had higher systolic BP (SBP) levels compared to AA homozygotes (sodium, p = 0.001; magnesium, p < 0.001). Also, individuals with the T allele for the rs1799722 polymorphism, with higher calcium intake, had significantly higher levels of SBP and diastolic BP (DBP) when compared to CC homozygotes (p = 0.037). In conclusion, our findings pointed for significant interactions between genetic polymorphisms (rs699-AGT and rs1799722-BDKRB2) and the consumption of micronutrients (sodium, magnesium, and calcium) on the BP variation. These findings contribute to the understanding of the complex mechanisms involved in BP regulation, which probable include several gene-nutrition interactions.

Distinct genetic subtypes of adiposity and glycemic changes in response to weight-loss diet intervention: the POUNDS Lost trial.

PURPOSE: Obesity is a heterogeneous condition and distinct adiposity subtypes may differentially affect type 2 diabetes risk. We assessed relations between genetically determined subtypes of adiposity and changes in glycemic traits in a dietary intervention trial. METHODS: The four genetic subtypes of adiposity including waist-hip ratio-increase only (WHRonly+), body mass index-increase only (BMIonly+), WHR-increase and BMI-increase (BMI+WHR+), and WHR-decrease and BMI-increase (BMI+WHR-) were assessed by polygenetic scores (PGSs), calculated based on 159 single nucleotide polymorphisms related to BMI and/or WHR. We examined the associations between the four PGSs and changes in fasting glucose, insulin, ß-cell function (HOMA-B) and insulin resistance (HOMA-IR) in 692 overweight participants (84% white Americans) who were randomly assigned to one of four weight-loss diets in a 2-year intervention trial. RESULTS: Higher BMI+WHR-PGS was associated with a greater decrease in 2-year changes in waist circumference in white participants (P = 0.002). We also found significant interactions between WHRonly+PGS and dietary protein in 2-year changes in fasting glucose and HOMA-B (P = 0.0007 and < 0.0001, respectively). When consuming an average-protein diet, participants with higher WHRonly+PGS showed less increased fasting glucose (ß = - 0.46, P = 0.006) and less reduction in HOMA-B (ß = 0.02, P = 0.005) compared with lower WHRonly+PGS. Conversely, eating high-protein diet was associated with less decreased HOMA-B among individuals with lower than higher WHRonly+PGS (ß = - 0.02, P = 0.006). CONCLUSIONS: Distinct genetically determined adiposity subtypes may differentially modify the effects of weight-loss diets on improving glucose metabolism in white Americans. This trial was registered at clinicaltrials.gov as NCT00072995.

Fruit intake, genetic risk and type 2 diabetes: a population-based gene-diet interaction analysis.

PURPOSE: Whether the association between fruit and type 2 diabetes (T2D) is modified by the genetic predisposition of T2D was yet elucidated. The current study is meant to examine the gene-dietary fruit intake interactions in the risk of T2D and related glycemic traits. METHODS: We performed a cross-sectional study in 11,657 participants aged ≥ 40 years from a community-based population in Shanghai, China. Fruit intake information was collected by a validated food frequency questionnaire by asking the frequency of consumption of typical food items over the previous 12 months. T2D-genetic risk score (GRS) was constructed by 34 well established T2D common variants in East Asians. The risk of T2D, fasting, 2 h-postprandial plasma glucose, and glycated hemoglobin A1c associated with T2D-GRS and each individual single nucleotide polymorphisms (SNPs) were tested. RESULTS: The risk of T2D associated with each 1-point of T2D-GRS was gradually decreased from the lower fruit intake level (< 1 times/week) [the odds ratio (OR) and 95% confidence interval (CI) was 1.10 (1.07-1.13)], to higher levels (1-3 and > 3 times/week) [the corresponding ORs and 95% CIs were 1.08 (1.05-1.10) and 1.07 (1.05-1.08); P for interaction = 0.04]. Analyses for associations with fasting, 2 h-postprandial plasma glucose and glycated hemoglobin A1c demonstrated consistent tendencies (all P for interaction ≤ 0.03). The inverse associations of fruit intake with risk of T2D and glucose traits were more prominent in the higher T2D-GRS tertile. CONCLUSIONS: Fruit intakes interact with the genetic predisposition of T2D on the risk of diabetes and related glucose metabolic traits. Fruit intake alleviates the association between genetic predisposition of T2D and the risk of diabetes; the association of fruit intake with a lower risk of diabetes was more prominent in population with a stronger genetic predisposition of T2D.

BDNF Gene as a Precision Skill of Obesity Management.

The scarcity of the results obtained for the treatment of obesity leads us to consider new strategies, contemplating all the factors involved in the development of the disease. One of the key molecules for controlling body weight and energy homeostasis is the brain-derived neurotrophic factor (BDNF). This work summarizes the mechanisms in which BDNF gene regulates this multifactorial disease. In addition, we discuss the role of other BDNF polymorphisms as genetic determinants of obesity. In this context, a total of 14 SNPs near or inside BDNF/BDNF-AS related to BMI were identified in various GWASs. Finally, we assess gene-diet interaction as a novel tool to prevent obesity and formulate solid and personalized nutritional management. Our research group has performed the first study on the association of BDNF-AS rs925946 polymorphism and calcium intake as potential modulators of the nutritional status. Although these results should be confirmed in future studies, they open the path for new prevention opportunities.

FTO gene-lifestyle interactions on serum adiponectin concentrations and central obesity in a Turkish population.

The aim of the study was to investigate whether lifestyle factors modify the association between fat mass and obesity-associated (FTO) gene single nucleotide polymorphisms (SNPs) and obesity in a Turkish population. The study included 400 unrelated individuals, aged 24-50 years recruited in a hospital setting. Dietary intake and physical activity were assessed using 24-hour dietary recall and self-report questionnaire, respectively. A genetic risk score (GRS) was developed using FTO SNPs, rs9939609 and rs10163409. Body mass index and fat mass index were significantly associated with FTO SNP rs9939609 (p = 0.001 and p = 0.002, respectively) and GRS (p = 0.002 and p = 0.003, respectively). The interactions between SNP rs9939609 and physical activity on adiponectin concentrations, and SNP rs10163409 and dietary protein intake on increased waist circumference were statistically significant (Pinteraction = 0.027 and Pinteraction = 0.044, respectively). Our study has demonstrated that the association between FTO SNPs and central obesity might be modified by lifestyle factors in this Turkish population.

Cocaine and amphetamine-regulated transcript prepropeptide gene (CARTPT) polymorphism interacts with Diet Quality Index-International (DQI-I) and Healthy Eating Index (HEI) to affect hypothalamic hormones and cardio-metabolic risk factors among obese individuals.

BACKGROUND: Epidemiologic studies show that cocaine- and amphetamine-regulated transcript prepropeptide (CARTPT) gene polymorphism modifies diet-obesity relationships. However, the interaction between CARTPT gene polymorphism and diet quality indices have not been investigated yet. The current study was aimed to evaluate the interaction between major dietary indices including Diet Quality Index-International (DQI-I) and Healthy Eating Index (HEI)-2015 and CARTPT gene rs2239670 variants among apparently healthy obese Iranians. METHODS: This cross-sectional study was carried out by employing 288 apparently healthy obese adults aged 20-50 years with a BMI of 30-40 kg/m2. Diet quality was evaluated by Diet Quality Index-International (DQI-I) and Healthy Eating Index-2015 (HEI-2015) using a 132-items semi-quantitative validated food frequency questionnaire. The CARTPT gene rs2239670 polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Blood concentrations of glycemic markers, lipid profile, α-melanocyte stimulating hormone (MSH) and agouti-related peptide (AgRP) were also measured. ANCOVA multivariate interaction model was used to analyze gene-diet interactions. RESULTS: The significant interactions were identified between CARTPT gene polymorphism and HEI, affecting BMR (PInteraction = 0.003), serum glucose (PInteraction = 0.009) and high density lipoprotein cholesterol HDL concentrations (PInteraction = 0.03) after adjusting for the effects of sex and age. Also we found gene-diet interaction between CARTPT genotypes and DQI-I in terms of fat mass (FM; PInteraction = 0.02), waist circumference (WC; PInteraction < 0.001), body mass index (BMI; PInteraction < 0.001), basal metabolic rate (BMR, PInteraction < 0.001), serum fasting glucose (PInteraction < 0.01) and AgRP (PInteraction = 0.05) in individuals even after adjusting for potential confounders. CONCLUSION: Current study showed the effects of interaction between CARTPT genotype with adherence to HEI and DQI-I scores on obesity-related anthropometric and metabolic risk-factors.