Significant Gene-diet Interactions Research Articles

Personalized Nutrition: Tailoring Dietary Recommendations through Genetic Insights.

Personalized nutrition (PN) represents a transformative approach in dietary science, where individual genetic profiles guide tailored dietary recommendations, thereby optimizing health outcomes and managing chronic diseases more effectively. This review synthesizes key aspects of PN, emphasizing the genetic basis of dietary responses, contemporary research, and practical applications. We explore how individual genetic differences influence dietary metabolisms, thus underscoring the importance of nutrigenomics in developing personalized dietary guidelines. Current research in PN highlights significant gene-diet interactions that affect various conditions, including obesity and diabetes, suggesting that dietary interventions could be more precise and beneficial if they are customized to genetic profiles. Moreover, we discuss practical implementations of PN, including technological advancements in genetic testing that enable real-time dietary customization. Looking forward, this review identifies the robust integration of bioinformatics and genomics as critical for advancing PN. We advocate for multidisciplinary research to overcome current challenges, such as data privacy and ethical concerns associated with genetic testing. The future of PN lies in broader adoption across health and wellness sectors, promising significant advancements in public health and personalized medicine.

Selection scan in Native Americans of Mexico identifies FADS2 rs174616: Evidence of gene-diet interactions affecting lipid levels and Delta-6-desaturase activity

Searching for positive selection signals across genomes has identified functional genetic variants responding to environmental change. In Native Americans of Mexico, we used the fixation index (Fst) and population branch statistic (PBS) to identify SNPs suggesting positive selection. The 103 most differentiated SNPs were tested for associations with metabolic traits, the most significant association was FADS2/rs174616 with body mass index (BMI). This variant lies within a linkage disequilibrium (LD) block independent of previously reported FADS selection signals and has not been clearly associated with metabolic phenotypes. We tested this variant in two independent cohorts with cardiometabolic data. In the Genetics of Atherosclerotic Disease (GEA) cohort, the derived allele (T) was associated with increased BMI, lower LDL-C levels and a decreased risk of subclinical atherosclerosis in women. Significant gene-diet interactions affected lipid, apolipoprotein and adiponectin levels with differences according to sex, involving mainly total and complex dietary carbohydrate%. In the Genotype-related Effects of PUFA trial, the derived allele was associated with lower Δ-6 desaturase activity and erythrocyte membrane dihomo-gamma-linolenic acid (DGLA) levels, and with increased Δ-5 desaturase activity and eicosapentaenoic acid levels. This variant interacted with dietary carbohydrate% affecting Δ-6 desaturase activity. Notably, the relationship of DGLA and other erythrocyte membrane LC-PUFA indices with HOMA-IR differed according to rs174616 genotype, which has implications regarding how these indices should be interpreted. In conclusion, this observational study identified rs174616 as a signal suggesting selection in an independent linkage disequilibrium block, was associated with cardiometabolic and erythrocyte measurements of LC-PUFA in two independent Mexican cohorts and showed significant gene-diet interactions.

Interactions between folate metabolism-related nutrients and polymorphisms on colorectal cancer risk: a case-control study in the Basque country

Folate-mediated one-carbon metabolism (FOCM) plays an important role in colorectal carcinogenesis. Previous studies have assessed the role of folate-mediated one-carbon metabolism (FOCM)-related gene-diet interaction in the aetiology of colorectal cancer (CRC), however, the results remained inconclusive. Thus, this study aimed to investigate dietary factors and genetic variants related to FOCM, as well as potential nutrient-gene and nutrient-lifestyle interactions, on CRC risk. This observational study included 229 patients diagnosed with CRC and 229 age- and sex-matched subjects as controls from a population-based bowel cancer screening program. Conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (95%CI) for CRC risk. A Bonferroni-corrected threshold of α = 0.005 was considered significant, and P values less than 0.05 were considered to be suggestive of an association. After Bonferroni correction, a high dietary intake of betaine was associated with a decreased risk of CRC in the adjusted model (OR, 95% CI: 0.21, 0.10–0.40, P < 0.001). Two SNPs, rs1476413 and rs17824591, exhibited significant gene-diet interactions with total choline ad vitamin B12 intakes, respectively, in adjusted models (total choline, tertile 3 vs. 1, OR, 95% CI: 0.25, 0.11–0.66, Pinteraction = 0.012; vitamin B12, tertile 2 vs. tertile 1, OR, 95% CI: 2.48, 1.04-5.00, Pinteraction = 0.003). These findings suggest that betaine intake and interactions between some dietary factors and variants in MTHFR and MTHFD1 genes have an influence on CRC risk in the population studied. If these results are confirmed, specific nutritional intervention strategies could be designed.

Interactions Between Genetic Risk Score and Healthy Plant Diet Index on Cardiometabolic Risk Factors Among Obese and Overweight Women.

People with higher genetic predisposition to obesity are more susceptible to cardiovascular diseases (CVDs) and healthy plant-based foods may be associated with reduced risks of obesity and other metabolic markers. We investigated whether healthy plant-foods-rich dietary patterns might have inverse associations with cardiometabolic risk factors in participants at genetically elevated risk of obesity. For this cross-sectional study, 377 obese and overweight women were chosen from health centers in Tehran, Iran. We calculated a healthy plant-based diet index (h-PDI) in which healthy plant foods received positive scores, and unhealthy plant and animal foods received reversed scores. A genetic risk score (GRS) was developed based on 3 polymorphisms. The interaction between GRS and h-PDI on cardiometabolic traits was analyzed using a generalized linear model (GLM). We found significant interactions between GRS and h-PDI on body mass index (BMI) (p = 0.02), body fat mass (p = 0.04), and waist circumference (p = 0.056). There were significant gene-diet interactions for healthful plant-derived diets and BMI-GRS on high-sensitivity C-reactive protein (p = 0.03), aspartate aminotransferase (p = 0.04), alanine transaminase (p = 0.05), insulin (p = 0.04), and plasminogen activator inhibitor 1 (p = 0.002). Adherence to h-PDI was more strongly related to decreased levels of the aforementioned markers among participants in the second or top tertile of GRS than those with low GRS. These results highlight that following a plant-based dietary pattern considering genetics appears to be a protective factor against the risks of cardiometabolic abnormalities.

Genetic variation in 9p21, dietary patterns, and insulin sensitivity.

Background: Single nucleotide polymorphisms in the 9p21 region have been associated with cardiovascular disease and to a lesser extent insulin sensitivity. Previous studies have focused on older populations, and few have examined the impact of gene-diet interactions. The objective of this study was to determine the interaction between dietary patterns and 9p21 genotypes on insulin sensitivity in young adults from different ethnic groups. Methods: Subjects were 1,333 participants aged 20–29 years from the Toronto Nutrigenomics and Health Study (405 men and 928 women; 776 Caucasians and 557 East Asians). Fasting blood was collected to measure glucose, insulin, c-reactive protein and serum lipids, as well as to isolate DNA for genotyping subjects for five SNPs in 9p21 (rs10757274, rs10757278, rs1333049, rs2383206, and rs4977574). Insulin resistance (HOMA-IR) and beta-cell dysfunction (HOMA-Beta) were calculated from fasting insulin and glucose concentrations. The Toronto-modified Harvard 196-item semi-quantitative food frequency questionnaire was used to measure dietary intake over 1 month and principal components analysis was used to identify three dietary patterns (Prudent, Western and Eastern). ANOVA and ANCOVA were used to examine gene-diet interactions on markers of insulin sensitivity. Results: Significant gene-diet interactions on insulin sensitivity using HOMA-IR were observed with all five SNPs, which remained significant after adjusting for covariates (p < 0.05). Among those who were homozygous for the 9p21 risk allele (rs1333049), fasting insulin was 40% higher in those who were consuming a low-prudent diet compared to those consuming a high-prudent diet (p < 0.05). No differences were observed between those following a low versus high-prudent diet among those who did not carry a 9p21 risk allele. Similar findings were observed with HOMA-Beta, however, the association was only significant for rs10757274 (p = 0.04). Conclusion: Our findings suggest that a prudent dietary pattern may protect against the effects of 9p21 risk genotypes on insulin sensitivity.

Healthy beverages may reduce the genetic risk of abdominal obesity and related metabolic comorbidities: a gene-diet interaction study in Iranian women

Background & aimsThe nutrition transition in developing countries like Iran causes the increasing rise of obesity and abdominal obesity rates. However, it is not yet well proven that environmental modifications like improving the quality of beverage intake can be effective in people who have a genetic predisposition to obesity. So, in the present study, we examine the interaction between genetic predisposition and healthy beverage index (HBI) with abdominal obesity and obesity-related metabolic risk factors in overweight and obese women.MethodBased on inclusion and exclusion criteria, 202 overweight or obese females were chosen for this cross-sectional study. Body composition, anthropometric measures, physical activity, and beverage intake data were collected and analyzed using recognized and trustworthy methodologies. Biochemical tests were performed on serum samples. A genetic risk score (GRS) was calculated based on the results of genetic tests. The predetermined HBI was calculated based on previous studies. A generalized linear model was used to estimate the interactions between GRS and HBI (GLM).ResultsWe found significant interactions between GRS and HBI on WHR (β = − 0.39, CI: -0.07 to 0.001, P = 0.05) and WC (β = − 6.18, CI: − 13.41 to 1.05, P = 0.09). Also, there were significant gene-diet interactions for HBI and GRS on HDL (β = 7.09, CI: − 0.73 to 14.92, P = 0.07) and FBS (β = − 9.07, CI: − 18.63 to 0.47, P = 0.06).ConclusionsThese findings emphasize the HBI considering genetics appears to protect against the risks of abdominal obesity and metabolic associated obesity markers.

Interaction of Cry1 Gene Polymorphisms and Dominant Food Patterns on Obesity: A Cross-Sectional Study.

Background:Evidence suggests that there is some relationship between circadian clock gene variants and obesity. However, there are few examinations supporting this observation in human subjects. This study was aimed to investigate the interaction between Cry1 circadian gene polymorphism and major dietary patterns on obesity measurements.Methods:Healthy overweight and obese women aged 18–53 years old were recruited from health centers in Tehran, Iran by a multistage cluster random sampling method (n = 377). Major dietary patterns were elicited after assessing the intake of 16 food groups using a valid and reliable 147-item food frequency questionnaire (FFQ). Anthropometric measurements were performed for each and every participant. Body composition was analyzed using bioelectrical impedance analysis (BIA). Socio-demographic and physical activity data were also collected by a validated Farsi demographic questionnaire and the international physical activity questionnaire (IPAQ). The Cry1 rs2287161 polymorphism were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Generalized linear models were used for interaction analysis.Results:Two major dietary patterns, including healthy and unhealthy dietary pattern (HDP and UDP, respectively) were determined using factor analysis. Our study showed a significant higher weight (P = 0.003), body mass index (BMI) (P = 0.042), hip circumference (P = 0.052), and body fat mass (P = 0.028) in carriers of C allele compared with G allele. Moreover, a significant gene-diet interaction was observed between being a carrier of C allele and BMI (P = 0.099 for CC genotype; P = 0.1 for CG genotype) and fat mass (P = 0.1 for CG genotype).Conclusions:The current study suggests a significant interaction of Cry1 rs2287161 gene polymorphisms in people following a healthy dietary pattern on BMI and fat mass among carriers of C allele compared to carriers of G allele.

Impact of dietary and obesity genetic risk scores on weight gain

Whether genetic background and/or dietary behaviors influence weight gain in middle-aged subjects is debated. To assess whether genetic background and/or dietary behaviors are associated with changes in obesity markers (BMI, weight, and waist and hip circumferences) in a Swiss population-based cohort. Cross-sectional and prospective (follow-up of 5.3 y) study. Two obesity genetic risk scores (GRS) based on 31 or 68 single nucleotide polymorphisms were used. Dietary intake was assessed using a semiquantitative FFQ. Three dietary patterns "Meat & fries" (unhealthy), "Fruits & vegetables" (healthy), and "Fatty & sugary" (unhealthy), and 3 dietary scores (2 Mediterranean and the Alternative Healthy Eating Index [AHEI]) were computed. On cross-sectional analysis (N=3033, 53.2% females, 58.4±10.6 y), obesity markers were positively associated with unhealthy dietary patterns and GRS, and negatively associated with healthy dietary scores and patterns. On prospective analysis (N=2542, 54.7% females, age at baseline 58.0±10.4 y), the AHEI and the "Fruits & vegetables" pattern were negatively associated with waist circumference gain: multivariate-adjusted average±SE 0.96±0.25 compared with 0.11±0.26 cm (P for trend 0.044), and 1.14±0.26 compared with -0.05±0.26 cm (P for trend 0.042) for the first and fourth quartiles of the AHEI and the "Fruits & vegetables" pattern, respectively. Similar inverse associations were obtained for changes in waist>5 cm: multivariate-adjusted OR (95% CI): 0.65 (0.50, 0.85) and 0.67 (0.51, 0.89) for the fourth versus the first quartile of the AHEI and the "Fruits & vegetables" dietary pattern, respectively. No associations were found between GRS and changes in obesity markers, and no significant gene-diet interactions were found. Dietary intake, not GRS, are associated with waist circumference in middle-aged subjects living in Lausanne, Switzerland.

Assessing Interactions between PNPLA3 and Dietary Intake on Liver Steatosis in Mexican-Origin Adults.

Mexican-origin (MO) adults have among the highest rates of nonalcoholic fatty liver disease (NAFLD) placing them at increased risk of liver cancer. Evidence suggests that a single nucleotide polymorphism (SNP) in the PNPLA3 gene, rs738409, increases the risk and progression of NAFLD and may modify the relationship between certain dietary factors and liver steatosis. The purpose of this study was to identify whether interactions exist between specific dietary factors and rs738409 genotype status among MO adults in relation to levels of liver steatosis. We analyzed cross-sectional data from a sample of 288 MO adults. Participants completed at least two 24-h dietary recalls. Multiple linear regression was performed assuming an additive genetic model to test the main effects of several dietary variables on levels of hepatic steatosis, adjusting for covariates. To test for effect modification, the product of the genotype and the dietary variable was included as a covariate in the model. No significant association between dietary intake and level of hepatic steatosis was observed, nor any significant gene-diet interactions. Our findings suggest that dietary intake may have the same magnitude of protective or deleterious effect even among MO adults with high genetic risk for NAFLD and NAFLD progression.

Interactions between Caveolin-1 (rs3807992) polymorphism and major dietary patterns on cardio-metabolic risk factors among obese and overweight women

BackgroundCaveolin-1 (CAV-1) is a cholesterol-dependent essential component located in caveolae. Several studies have been CAV-1 related to cardio-metabolic parameters in animal models, however, there are few studies in humans. Importantly, there is no study has investigated the interaction between CAV-1 rs3807992 gene and dietary patterns (DPs) on cardio-metabolic risk factors.MethodsThe current cross-sectional study was conducted on 404 overweight and obese women. Dietary intake was obtained from FFQ with 147 items. The CAV-1 genotype was measured by the PCR-RFLP method. The anthropometric measurements, serum lipid profile, and inflammatory markers were measured by standard protocols.ResultsThere was a significant interaction between CAV-1 rs3807992 and healthy DP on high-density cholesterol (HDL) (P-interaction = 0.03), TC/HDL (P-interaction = 0.03) and high sensitivity C-reactive protein (hs-CRP) (P-interaction = 0.04); in A-allele carriers, higher following a healthy DP was related to a higher level of HDL and lower TC/HDL and hs-CRP. As well as, the significant interactions were observed between CAV-1 rs3807992 and unhealthy DP in relation to triglyceride (TG) (P-interaction = 0.001), aspartate aminotransferase (AST) (P-interaction = 0.01) and monocyte chemoattractant protein-1(MCP-1) (P-interaction = 0.01); A-allele carriers were more following the unhealthy DP had lower levels of TG, AST and MCP-1.ConclusionsOur study revealed a significant gene-diet interaction between rs3807992 SNPs and DPs in relation to cardio-metabolic risk factors; A-allele carriers might be more sensitive to dietary composition compared to GG homozygotes. Following a healthy DP in A-allele-carriers may be improved their genetic association with cardio-metabolic risk factors.

Variants in Circadian Rhythm Gene Cry1 Interacts with Healthy Dietary Pattern for Serum Leptin Levels: a Cross-sectional Study.

Circadian disruption causes obesity and other metabolic disorders. There is no research considering the role of Cryptochromes (Cry) 1 body clock gene and major dietary patterns on serum leptin level and obesity. We aimed to investigate the interaction between Cry1 circadian gene polymorphisms and major dietary patterns on leptin and obesity related measurements. This study was performed on 377 overweight and obese women. Mean age and body mass index (BMI) of study subjects were 36.64 ± 9.02 years and 30.81 ± 3.8 kg/m2, respectively. Dietary assessment was done using a validated 147-item food frequency questionnaire. Cry1 rs2287161 were genotyped using polymerase chain reaction-restriction fragment length polymorphism. Generalized linear models were used for interaction analysis. Healthy and unhealthy dietary pattern (HDP and UDP, respectively) were extracted using factor analysis (principal component analysis). Our study revealed a significant higher weight (p = 0.003) and BMI (p = 0.042) in women carrying CC homozygote compared with G allele carriers. Moreover, our findings showed a significant gene-diet interaction between HDP and Cry1 rs2287161 on BMI (p = 0.034) and serum leptin level (p = 0.056) in which, BMI and serum leptin level were lower in subjects with CC genotype than in those with GG genotype while following HDP. This study suggests a significant interaction between Cry1 rs2287161 polymorphisms and HDP on BMI and serum leptin and the lowering effects were apparent among C allele carriers compared to G allele ones. This data highlights the role of dietary pattern in relation of gene and obesity.

FADS Genetic Variants in Taiwanese Modify Association of DHA Intake and Its Proportions in Human Milk.

Our objective was to determine how docosahexaenoic acid (DHA) proportions in human milk are modulated by maternal FADS gene variants and dietary intake in Taiwanese women. Inclusion criteria included being healthy, 20–40 y old, having had a full-term baby that they intended to breast feed for at least 1 month, and willingness to participate in this study. Intake of DHA was assessed by food frequency questionnaire and fatty acids were analyzed in human milk samples collected 3–4 weeks postpartum. Based on multiple linear regression of data from 164 mothers that completed this study, there was 0.28% (FA%) reduction in milk DHA in high versus low genetic risk (stratified by whether minor allele numbers were ≥ 3 in rs1535 and rs174448) and 0.45% reduction in low versus high intake (stratified by whether DHA intake reached 200 mg/d). There was a significant gene–diet interaction; mothers with low genetic risk only had high milk DHA proportions with high DHA intake, whereas for mothers with high genetic risk, dietary effects were quite limited. Therefore, for FADS single nucleotide polymorphism in Taiwanese women, increasing DHA intake did not correct low milk DHA proportions in those with a high-risk genotype. Diet only conferred benefits to those with a low-risk genotype. Trial registration: This trial was retrospectively registered (Feb 12, 2019) in ClinicalTrials.gov (No. NCT03842891, https://clinicaltrials.gov/ct2/show/NCT03842891).

Dietary quality indices modifies the effects of melanocortin-4 receptor (MC4R) rs17782313 polymorphism on cardio-metabolic risk factors and hypothalamic hormones in obese adults

BackgroundAlthough the Melanocortin-4 Receptor (MC4R) gene rs17782313 C/T has been consistently related to obesity risk, the interaction between MC4R polymorphism and diet quality indices on cardio-metabolic risk factors has not yet investigated. Therefore we aimed to test this hypothesis.MethodsThis cross-sectional study recruited 188 (96 males and 92 females) healthy obese adults aged 20–50 years. Diet quality indices including Healthy Eating Index-2015 (HEI-2015) and Diet Quality Index-International (DQI-I) were constructed using data from a validated food frequency questionnaire. MC4R s17782313 were genotyped by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). The interaction between MC4R polymorphism and diet quality indices was tested by Analysis of covariance (ANCOVA) multivariate interaction model.ResultsThere were significant gene-diet interactions between rs17782313 and HEI-2015 (P Interaction < 0.05) in modulating low-density lipoprotein cholesterol (LDL-C) levels among female group; rare allele heterozygotes of rs17782313 had highest mean of LDL-C concentration when placed in second tertile of HEI (P < 0.05). Moreover, rs17782313 and both indices (HEI and DQI-I) had significant interaction on serum glucose concentrations, systolic and diastolic blood pressure (SBP, DBP) in males (P Interaction < 0.05); when adherence to these indices was low, the obesity risk allele was associated with serum glucose concentrations, SBP and DBP. These gene-diet interactions remained significant even after adjustment for potential confounders.ConclusionOur study showed that MC4R rs17782313 interacts with adherence to the dietary quality indices (HEI and DQI-I) to influence several cardio-metabolic risk factors in obese male and females. Further large prospective studies are warranted to confirm our findings.

Cholesteryl ester transfer protein gene variations and macronutrient intakes interaction in relation to metabolic syndrome: Tehran lipid and glucose study.

Objective(s):There are controversial results regarding the effect of the interaction of CETP polymorphisms with dietary fats on the lipid profiles. The aim of this study was to examine the effect of CETP polymorphisms (rs5882 and rs3764261) and macronutrient intakes interaction in relation to metabolic syndrome (MetS) or its components.Materials and Methods:In this nested case-control study, subjects were selected from among participants of the Tehran Lipid and Glucose Study. Cases (n=441) were individually matched with two controls (844 non-MetS subjects). DNA samples were genotyped with HumanOmniExpress-24-v1-0 bead chips, including 649,932 SNP loci.Results:The mean ages at baseline were 38.1±10 and 37.0±10 years in women and 36.2±11 and 36.3±11 years in men, respectively in cases and controls. We did not find significant gene-diet interactions between rs5882 and dietary macronutrient intakes in relation to MetS risk. The risk of low HDL-C was lower in the first quartile of MUFA and total fat intake in G allele carriers, compared to AA genotype group. The risk of high BP appeared to increase significantly in higher quartiles of trans-fatty acid intakes (>1.81% of total energy intake) in G allele carriers compared with the AA genotype group. No significant interactions were found between rs3764261 and macronutrient intakes in association with MetS or its components.Conclusion:Our findings demonstrate that dietary fats modify the association of rs5882 and risk of low HDL-C and high blood pressure.

Dietary fat modulation of hepatic lipase variant -514 C/T for lipids: a crossover randomized dietary intervention trial in Caribbean Hispanics.

The hepatic lipase (LIPC) locus is a well-established determinant of high-density lipoprotein cholesterol (HDL-C) concentrations, an association that is modified by dietary fat in observational studies. Dietary interventions are lacking. We investigated dietary modulation of LIPC rs1800588 (-514 C/T) for lipids and glucose using a randomized crossover design comparing a high-fat Western diet and a low-fat traditional Hispanic diet in individuals of Caribbean Hispanic descent (n = 42, 4 wk/phase). No significant gene-diet interactions were observed for HDL-C. However, differences in dietary response according to LIPC genotype were observed. In major allele carriers (CC/CT), HDL-C (mmol/l) was higher following the Western diet compared with the Hispanic diet: phase 1 (Western: 1.3 ± 0.03; Hispanic: 1.1 ± 0.04; P = 0.0004); phase 2 (Western: 1.4 ± 0.03; Hispanic: 1.2 ± 0.03; P = 0.0003). In contrast, HDL-C in TT individuals did not differ by diet. Only major allele carriers benefited from the higher-fat diet for HDL-C. Secondarily, we explored dietary fat quality and rs1800588 for HDL-C and triglycerides (TG) in a Boston Puerto Rican Health Study (BPRHS) subset matched for diabetes and obesity status (subset n = 384). In the BPRHS, saturated fat was unfavorably associated with HDL-C and TG in rs1800588 TT carriers. LIPC rs1800588 appears to modify plasma lipids in the context of dietary fat. This new evidence of genetic modulation of dietary responses may inform optimal and personalized dietary fat advice and reinforces the importance of studying genetic markers in diet and cardiometabolic health.

Association and Interaction Effect of AGTR1 and AGTR2 Gene Polymorphisms with Dietary Pattern on Metabolic Risk Factors of Cardiovascular Disease in Malaysian Adults.

Gene-diet interaction using a multifactorial approach is preferred to study the multiple risk factors of cardiovascular disease (CVD). This study examined the association and gene-diet interaction effects of the angiotensin II type 1 receptor (AGTR1) gene (rs5186), and type 2 receptor (AGTR2) gene (rs1403543) polymorphisms on metabolic risk factors of CVD in Malaysian adults. CVD parameters (BMI, blood pressure, glycated hemoglobin, total cholesterol (TC), triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), and TC/HDL-C ratio), and constructed dietary patterns “vegetables, fruits, and soy diet” (VFSD), and “rice, egg, and fish diet” (REFD) were obtained from previous studies. Genotyping analysis was performed by real-time PCR using Taqman probes. The subjects were 507 adults (151 Malays; 179 Chinese; and 177 Indians). Significant genetic associations were obtained on blood lipids for rs5186 in Malays and Chinese, and rs1403543 in Chinese females. The significant gene-diet interaction effects after adjusting for potential confounders were: rs5186 × VFSD on blood pressure in Malays (p = 0.016), and in Chinese on blood lipids for rs5186 × REFD (p = 0.009–0.023), and rs1403543 × VFSD in female subjects (p = 0.001–0.011). Malays and Chinese showed higher risk for blood pressure and/or lipids involving rs5186 and rs1403543 SNPs together with gene-diet interactions, but not Indians.

Effect of the interaction between diet composition and the PPM1K genetic variant on insulin resistance and β cell function markers during weight loss: results from the Nutrient Gene Interactions in Human Obesity: implications for dietary guidelines (NUGENOB) randomized trial

Background: Circulating branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs) have been shown to be associated with insulin resistance and diabetes risk. The common rs1440581 T allele in the protein phosphatase Mg2+/Mn2+ dependent 1K (PPM1K) gene has been related to elevated BCAA concentrations and risk of type 2 diabetes.Objective: In the present study, we tested whether dietary fat and carbohydrate intakes influenced the association between the rs1440581 PPM1K genetic variant and glucose-metabolism traits during weight loss.Design: The rs1440581 PPM1K genetic variant was genotyped in a total of 757 nondiabetic individuals who were randomly assigned to 1 of 2 energy-restricted diets that differed in macronutrient composition (low-fat diet: 20-25% fat, 15% protein, and 60-65% carbohydrate; high-fat diet: 40-45% fat, 15% protein, and 40-45% carbohydrate). The changes in fasting glucose, fasting insulin, insulin resistance (homeostasis model assessment of insulin resistance) and homeostasis model assessment of β cell function (HOMA-B) were measured after a mean ± SD weight loss of 6.8 ± 3.4 kg over 10 wk and analyzed according to the presence of the T allele of rs1440581.Results: The rs1440581 T allele was associated with a smaller improvement in glucose concentrations after the 10-wk dietary intervention (β ± SE: 0.05 ± 0.02 mg/dL; P = 0.03). In addition, significant gene-diet interactions were shown for the rs1440581 PPM1K genetic variant in relation to changes in insulin and HOMA-B (P-interaction = 0.006 and 0.002, respectively). In response to the high-fat diet, the T allele was associated with a higher reduction of insulin (β ± SE: -0.77 ± 0.40 μU/mL; P = 0.04) and HOMA-B (β ± SE: -13.2 ± 3.81; P = 0.003). An opposite effect was observed in the low-fat diet group, although in this group the T allele was marginally (P = 0.10) and not significantly (P = 0.24) associated with insulin and HOMA-B, respectively.Conclusion:PPM1K rs1440581 may affect changes in glucose metabolism during weight loss, and this effect is dependent on dietary fat and carbohydrate intakes. This trial was registered at controlled-trials.com as ISRCTN25867281.

Novel polymorphism in FADS1 gene and fish consumption on risk of oral cancer: A case-control study in southeast China.

The aim of this study was to investigate the independent and combined effects of fatty acid desaturase 1 (FADS1) gene polymorphism and fish consumption on oral cancer. A hospital-based case-control study was performed including 305 oral cancer patients and 579 cancer-free controls. The genotypes were determined by TaqMan genotyping assay. Non-conditional logistic regression model was used to assess the effects of FADS1 rs174549 polymorphism and fish intake. Subjects carrying A allele of rs174549 significantly reduced the risk of oral cancer (AA VS GG, OR: 0.65, 95% CI: 0.42-0.99; AA VS AG+GG, OR: 0.67, 95% CI: 0.46-0.98). Moreover, the statistically significant reverse associations were especially evident in men, smokers, alcohol drinkers and those age ≤ 60 years. Additionally, fish intake ≥7 times/week showed a 73% reduction in risk for oral cancer compared to those who ate fish less than 2 times/week (OR: 0.27, 95% CI: 0.18-0.42). Furthermore, a significant gene-diet multiplicative interaction was observed between FADS1 rs174549 polymorphism and fish intake for oral cancer (P=0.028). This preliminary study suggests that FADS1 rs174549 polymorphism and fish consumption may be protective factors for oral cancer, with a gene-diet multiplicative interaction. Functional studies with larger samples are required to confirm our findings.

Beneficial effect of CETP gene polymorphism in combination with a Mediterranean diet influencing lipid metabolism in metabolic syndrome patients: CORDIOPREV study

The cholesteryl ester transfer protein (CETP) gene has been implicated in high-density lipoprotein (HDL-C) metabolism. However, little is known about the impact of this gene on metabolic syndrome (MetS) patients and its interaction with diet. Here, we evaluate whether the consumption of a Mediterranean diet, compared with a Low-fat diet, interacts with the rs3764261 SNP at the CETP locus to modify lipid metabolism in MetS patients. Plasma lipid concentrations and rs3764261 genotypes were determined in 424 MetS subjects participating in the CORDIOPREV clinical trial (NCT00924937). Gene-diet interactions were analyzed after a year of dietary intervention (Mediterranean diet (35% fat, 22% MUFA) vs Low-fat diet (28% fat, 12% MUFA)). We found significant gene-diet interactions between rs3764261 SNP and the dietary pattern for HDL-C (P=0.006) and triglyceride concentrations (P=0.040). Specifically, after 12 months of Mediterranean diet intervention, subjects who were carriers of the minor T allele (TT+TG) displayed higher plasma HDL-C concentrations (P=0.021) and lower triglycerides (P=0.020) compared with those who were homozygous for the major allele (GG). In contrast, in the Low-fat intervention group, no significant differences were found between CETP genotypes after 12 months of dietary treatment. Our data support the notion that the consumption of a Mediterranean diet may play a contributing role in triggering lipid metabolism by interacting with the rs3764261 SNP at CETP gene locus in MetS patients. Due to the complex nature of gene-environment interactions, dietary adjustment in MetS patients may require a personalized approach.

Gene‐diet interaction of a common FADS1 variant with marine polyunsaturated fatty acids for fatty acid composition in plasma and erythrocytes among men

Limited information exists on how the relationship between dietary intake of fat and fatty acids in erythrocytes and plasma is modulated by polymorphisms in the FADS gene cluster. We examined gene-diet interaction of total marine PUFA intake with a known gene encoding Δ-5 desaturase enzyme (FADS1) variant (rs174550) for fatty acids in erythrocyte membranes and plasma phospholipids (PL), cholesteryl esters (CE), and triglycerides (TG). In this cross-sectional study, fatty acid compositions were measured using GC, and total intake of polyunsaturated fat from fish and fish oil was estimated using a food frequency questionnaire in a subsample (n = 962) of the Metabolic Syndrome in Men Study. We found nominally significant gene-diet interactions for eicosapentaenoic acid (EPA, 20:5n-3) in erythrocytes (pinteraction = 0.032) and for EPA in plasma PL (pinteraction = 0.062), CE (pinteraction = 0.035), and TG (pinteraction = 0.035), as well as for docosapentaenoic acid (22:5n-3) in PL (pinteraction = 0.007). After excluding omega-3 supplement users, we found a significant gene-diet interaction for EPA in erythrocytes (pinteraction < 0.003). In a separate cohort of the Kuopio Obesity Surgery Study, the same locus was strongly associated with hepatic mRNA expression of FADS1 (p = 1.5 × 10(-10) ). FADS1 variants may modulate the relationship between marine fatty acid intake and circulating levels of long-chain omega-3 fatty acids.