Table 2. Summary of studies investigating the effect of interactions between the Mediterranean diet and genetic variants on obesity and obesity-related traits.
| Reference | Genes | Type of genetic variant | Study design | Population (n) | Phenotype | Diet | Interaction |
|---|---|---|---|---|---|---|---|
| Razquin et al. ( 134 ) | ADIPOQ | SNP (rs1501299 G>T) | RCT | Spain, high cardiovascular risk, adults (737) | Delta-Body weight | 3-years intervention with the Mediterranean diet vs. Control diet | Men with the TT genotype had higher body weight gain (vs. G allele carrier) after the intervention. The Mediterranean diet canceled the effect of genotype on body weight gain. |
| Razquin et al. ( 134 ) | ADIPOQ | SNP (rs2241766 T>G) | RCT | Spain, high cardiovascular risk, adults (737) | Delta-Body weight | 3-years intervention with the Mediterranean diet vs. Control diet | No interactions were found |
| Sánchez-Moreno et al. ( 135 ) | APOA5 | SNP (rs662799 T>C) | Cross-sectional | Spain, overweight or obese, adults (1465) | BMI (kg/m 2 ), body fat (%), Waist circumference (cm), hip (cm) | Macronutrient profile of the diet | Only TT carriers had a higher BMI, waist and hip circumferences when their diets were high in total fat and saturated fat. |
| Garaulet et al. ( 136 ) | CLOCK | SNP (rs4580704 C>G) | Non-RCT | Spain, overweight or obese, adults (454) | Weight (kg), BMI (kg/m 2 ), body fat (%), waist and hip circumference (cm) | 28-weeks hypocaloric Mediterranean diet advice and maintenance protocol | No interactions were found |
| Garaulet et al. ( 136 ) | CLOCK | SNP(rs1801260 A>G) | Non-RCT | Spain, overweight or obese, adults (454) | Weight (kg), BMI (kg/m 2 ), body fat (%), waist and hip circumference (cm) | 28-weeks hypocaloric Mediterranean diet advice and maintenance protocol | G allele carriers had higher BMI at baseline and were less successful in losing weight after the intervention period. |
| Garaulet et al. ( 136 ) | CLOCK | SNP(rs3749474 C>T) | Non-RCT | Spain, overweight or obese, adults (454) | Weight (kg), BMI (kg/m 2 ), body fat (%), waist and hip circumference (cm) | 28-weeks hypocaloric Mediterranean diet advice and maintenance protocol | No interactions were found. |
| Corella & Ordovas ( 137 ) | FAIM2 | SNP (rs7138803 G>A) | RCT | Spain, high cardiovascular risk, adults (7161) | BMI (kg/m 2 ), body weight (kg), and waist circumference (cm) | 4.8-years intervention with the Mediterranean diet vs. Control diet | No interactions were found |
| Hosseini-Esfahani, et al. ( 45 ) | FTO | SNP(rs1121980 G>A) | Nested case-control study | Iran, adults (627 cases and 1,254 controls) | Obesity (BMI cut-off) and abdominal obesity (waist circumference and waist-to-hip ratio cut-offs) | Mediterranean diet score | No interactions were found |
| Hosseini-Esfahani, et al. ( 45 ) | FTO | SNP(rs1421085 T>C) | Nested case-control study | Iran, adults (627 cases and 1,254 controls) | Obesity (BMI cut-off) and abdominal obesity (waist circumference and waist-to-hip ratio cut-offs) | Mediterranean diet score | No interactions were found |
| Hosseini-Esfahani, et al. ( 45 ) | FTO | SNP(rs1781749 T>G) | Nested case-control study | Iran, adults (627 cases and 1,254 controls) | Obesity (BMI cut-off) and abdominal obesity (waist circumference and waist-to-hip ratio cut-offs) | Mediterranean diet score | Only G allele carriers had decreased odds for obesity and abdominal obesity when in the highest quartiles of the Mediterranean diet score. |
| Hosseini-Esfahani, et al. ( 45 ) | FTO | SNP(rs3751812 G>T) | Nested case-control study | Iran, adults (627 cases and 1,254 controls) | Obesity (BMI cut-off) and abdominal obesity (waist circumference and wais-to-hip ratio cut-offs) | Mediterranean diet score | Only T allele carriers had decreased odds for obesity and abdominal obesity when in the highest quartiles of the Mediterranean diet score. |
| Hosseini-Esfahani, et al. ( 45 ) | FTO | SNP(rs8050136 G>A) | Nested case-control study | Iran, adults (627 cases and 1,254 controls) | Obesity (BMI cut-off) and abdominal obesity (waist circumference and wais-to-hip ratio cut-offs) | Mediterranean diet score | Only A allele carriers had decreased odds for obesity and abdominal obesity when in the highest quartiles of the Mediterranean diet score. |
| Corella et al. ( 138 ) | FTO | SNP(rs9939609 C>A) | Cross-sectional | Spain, high cardiovascular risk, adults (7,052) | BMI (kg/m 2 ), body weight (kg), and waist circumference (cm) | Adherence do the Mediterranean diet | No interactions were found |
| Roswall et al. ( 139 ) | FTO | SNP(rs9939609 C>A) | Nested case-control study | Europe, adults (5,552 cases and 5,496 controls) | Delta-Body weight, and Delta-Waist circumference | Mediterranean diet score | No interactions were found |
| Razquin et al. ( 134 ) | FTO | SNP(rs9939973 G>A) | RCT | Spain, high cardiovascular risk, adults (776) | BMI (kg/m 2 ), body weight (kg), and waist circumference (cm) | 3-years intervention with the Mediterranean diet vs. Control diet | A allele carriers had the lowest body omozy gain (vs. GG genotype) after the intervention with the Mediterranean diet. This difference was not observed in individuals omozygou to the control diet intervention. |
| Hosseini-Esfahani, et al. ( 45 ) | FTO | SNP(rs9939973 G>A) | Nested case-control study | Iran, adults (627 cases and 1,254 controls) | Obesity (BMI cut-off) and abdominal obesity (waist circumference and wais-to-hip ratio cut-offs) | Mediterranean diet score | Only A allele carriers had decreased odds for obesity when in the highest quartiles of the Mediterranean diet score. |
| Corella et al. ( 138 ) | MC4R | SNP(rs17782313 T>C) | Cross-sectional | Spain, high cardiovascular risk, adults (7,052) | BMI (kg/m 2 ), body weight (kg), and waist circumference (cm) | Adherence do the Mediterranean diet | No interactions were found |
| de Luis et al. ( 140 ) | MTNR1B | SNP(rs10830963 C>G) | Non-RCT | Spain, obese, adults ( 80 ) | BMI (kg/m 2 ), body weight (kg), fat mass (g), waist circumference (cm) | 12-weeks intervention wih hypocaloric Mediterranean diet | The improvement of the anthropometric parameters after the intervention was higher among CC cariers (vs. G allele carriers). |
| Garaulet et al. ( 141 ) | PPARG | SNP(rs1801282 C>G) | Non-RCT | Spain, overweight or obese, adults | Delta-Body weight | Behavioural treatment program for obesity based on a Mediterranean diet (duration varied according to patients need) | G allele carriers had less weight loss when fat intake was above 42.6% of total energy intake, in comparison do CC homozygotes. |
| Roswall et al. ( 139 ) | TCF7L2 | SNP(rs7903146 C>T) | Nested case-control study | Europe, adults (5,552 cases and 5,496 controls) | Delta-Body weight, and Delta-Waist circumference | Mediterranean diet score | Only when the Mediterranean diet score was high, there was a lower weight gain in TT omozygous, in comparison to C allele carriers. |
| Barchitta et al. ( 142 ) | TNF | SNP(rs1800629 G>A) | Cross-sectional | Italy, women only, adults (380) | Overweight and obesity (BMI cut-off) | Mediterranean diet score | No interactions were found |
| Corella et al. ( 138 ) | FTO, MC4R | 2-SNP GRS | Cross-sectional | Spain, high cardiovascular risk, adults (7,052) | BMI (kg/m 2 ), body weight (kg), and waist circumference (cm) | Adherence do the Mediterranean diet | No interactions were found |
| Garaulet et al. ( 143 ) | CLOCK, SIRT1 | 2-SNP GRS | Non-RCT | Spain, overweight or obese, adults (1,465) | Delta-Body weight (kg) | 40-weeks intervention with dietary advice to loose weight, based in the Mediterranean diet | Individuals with higher GRS lost less body weight than individuals with lower GRS after the intervention period |
| Frankwich et al. ( 144 ) | APOA2, ADIPOQ, FTO, KCTD10, LIPC, MMAB, PPARG | 7-SNP GRS | RCT | US, men only, adults ( 51 ) | proportion of individuals achieving at least 5% body weight loss | 8-weeks and 24-weeks genetic-guided dietary advice vs. Standard dietary advice | No difference was observed between the interventions |
| Hosseini-Esfahani et al. ( 45 ) | FTO | 6-SNP GRS | Nested case-control study | Iran, adults (627 cases and 1,254 controls) | Obesity (BMI cut-off) and abdominal obesity (waist circumference and wais-to-hip ratio cut-offs) | Mediterranean diet score | The odds for obesity decreased across quartiles of the Mediterranean diet score only in individuals with GRS ≥ 6. No interaction was found for abdominal obesity traits. |
| San-Cristobal et al. ( 36 ) | ADRB2, APOA5, APOE, BCMO1, COMT, GC, GPX1, MTHFR, SLCA4, SOD2, TCF7L2, TPH2, VDR | 14-SNP GRS | RCT | Europe, adults (1,263) | BMI (kg/m 2 ) and waist circumference (cm) | 6-month personalized dietary advice based in Mediterranean diet | No interactions were found. |
| Ding et al. ( 145 ) | Near 158 genes associated with BMI | 97-SNP GRS | 3-Longitudinal cohorts (pooled) | US, adults (31,058) | BMI (kg/m 2 ) | Alternative Mediterranean diet score | Individuals in the highers tertile of the alternative Mediterranean diet score had lower increases in BMI per 10 risk allele increase of the GRS |
| Ding et al. ( 145 ) | Near 102 genes associated with BMI and highly expressed in central nervous system | 54-SNP GRS | 3-Longitudinal cohorts (pooled) | US, adults (31,058) | BMI (kg/m 2 ) | Alternative Mediterranean diet score | Individuals in the highers tertile of the alternative Mediterranean diet score had lower increases in BMI per 10 risk allele increase of the GRS |
| Ding et al. ( 145 ) | Near 56 genes associated with BMI and highly expressed in tissues other than the central nervous system | 43-SNP GRS | 3-Longitudinal cohorts (pooled) | US, adults (31,058) | BMI (kg/m 2 ) | Alternative Mediterranean diet score | No interactions were found |
| Hennein et al. ( 146 ) | Intergenic, long non-coding RNA, regulatory regions | 4-SNP GRS | Longitudinal cohort | US, adults (1,677) | pericardial fat depots | Mediterranean diet score | Only individuals in the high-GRS cathegory had increased pericardial fat depot when Mediterranean diet score decreased during the follow-up period |
| Hennein et al. ( 146 ) | Intergenic, long non-coding RNA | 2-SNP GRS | Longitudinal cohort | US, adults (1,677) | visceral fat depots | Mediterranean diet score | No interactions were found. |
| Hennein et al. ( 146 ) | FTO, ATXN1 | 3-SNP GRS | Longitudinal cohort | US, adults (1,677) | subcutaneous fat depots | Mediterranean diet score | No interactions were found. |
BMI: body mass index; GRS: genetic risk score; RCT: randomized clinical trial; SNP: single nucleotide polymorphism. The same study was included more than once when more than one SNP was evaluated separately.