Table 1.
Observational studies analyzing n-3 fatty acids and genetic variants in determining intermediate phenotypes
| Reference | Study population | Phenotype | Genetic variant (s) | Interaction | Main results |
|---|---|---|---|---|---|
| Tai et al.(23) | Cross-sectional study in participants in the Framingham Offspring Study (1003 men and 1103 women) | Plasma triglycerides and apoC-III concentrations | PPARA (L162V polymorphism) | Yes PPARA L162V and n-3 fatty acids on plasma apoCIII concentrations |
Carriers of the 162V allele had significantly lower plasma triglycerides and apoC-III concentrations when consuming a high PUFA diet, in which n-3 and n-6 fatty acids seem to have a similar role. |
| Chan et al.(24) | Cross-sectional study among Participants in the 1998 Singapore National Health Survey: 1964 men (1318 Chinese, 364 Malays and 282 Asian Indians) and 2284 women (1581 Chinese, 397 Malays and 306 Asian Indians) | Plasma lipids | PPARA (V227A polymorphism) | Yes PPARA V227A and PUFA on HDL-C concentrations |
In carriers of the A227 allele, increasing PUFA intake was associated with lower HDL-C concentrations. In those who were homozygous for the common allele, this association was much weaker |
| Volcik et al.(25) | Cross-sectional study among participants in the biethnic Atherosclerosis Risk in Communities (ARIC) Study (10 134 whites and 3480 African Americans) | Plasma lipids | PPARA (L162V and 3′UTR C → T polymorphisms) | Yes PPARA 3′UTR C → T SNP and long-chain n-3 fatty acids on LDL-C |
A significant interaction between the PPARA 3′UTR C → T SNP and LC n-3 fatty acids on total cholesterol and LDL-C concentrations in African American participants. No significant interaction with the PPARA L126V SNP. |
| Lai et al.(26) | Cross-sectional study among participants in the Framingham Off-spring cohort (1001 men and 1147 women) | Plasma lipids, remnant-like particle concentrations, and lipoprotein particle size | APOA5 SNP: −1131T > C, −3A > G, IVS3 + 476G > A, and 1259T > C and 56C > G | No with n-3 fatty acids | Significant gene-diet interactions between the −1131T > C polymorphism and total PUFA intake were found in determining fasting triglycerides, remnants and particle size. However, the PUFA-APOA5 interactions were specific for dietary n-6 fatty acids. No significant interaction with n-3 fatty acids were found |
| Verduci et al.(27) | Cross-sectional study in obese children (53 girls and 68 boys) | Plasma adiponectin and HOMA-IR | ADIPOQ gene (SNP 276G > T) | Yes ADIPOQ polymorphism and n-6/n-3 LC-PUFA |
In obese children, carriers of the SNP 276G > T may be at increased risk of metabolic complications compared with noncarriers, possibly due in part to the n-6/n-3 LC-PUFA ratio in phospholipids |
| Ylönen et al.(28) | Cross-sectional estudy among 571 non-diabetic relatives of subjects with type II diabetes. | Plasma glucose and IR | PPARG2 (Pro12Ala SNP) | Yes Pro12Ala and intake of n-3 |
The PPARG polymorphism modulate the associations marine n-3 fatty acids with glucose metabolism and fasting free fatty acids |
| Lu et al.(29) | Cross-sectional investigation in the Doetinchem Cohort Study (3575 subjects) | Plasma lipids | FADS cluster (rs174546, rs482548, and rs174570 polymorphisms) | Yes rs174546 polymorphism and n-3 PUFA intake |
Significant associations between rs174546 genotypes and total and non-HDL- cholesterol concentrations in the group with a high intake of n-3 PUFA but not in the low intake group |
| Kim et al.(30) | Cross-sectional study in Koreans (580 men, 614 women). | Serum phospholipids, adiponectin, HOMA-IR | ADIPOQ: (−11391G > A; −11377C > G; H241P; Y111H;G90S; R221S; 45T > G; 276G > T polymorphisms) | No with n-3 | The 276G carriers with a higher proportion of 18:2n6 exhibited more pronounced IR characteristics. No interaction with n-3 was observed |
| Zhou et al.(31) | Cross-sectional study in Chinese (195 men and 386 women). Erythrocyte membrane fatty acids were measured |
Inflammatory markers | IL-6 (−572 C > G polymorphism) | Yes (IL-6 genotype and n-3 levels in males) |
Erythrocyte n-3 PUFA intake modulated the effects of IL-6 -572 genotype on HDL-c concentrations in males but not in females |
| Enzenbach et al.(32) | Cross-sectional study in 1980 participants of the European Prospective Investigation into Cancer and Nutrition (EPIC)- Potsdam cohort | CRP and adiponectin | PARG2 (Pro12Ala polymorphism) | No | Erythrocyte PUFA are related to circulating CRP and adiponectin. However, these associations were not modified by the PPARG2 Pro12Ala polymorphism |
| Huang et al.(33) | Cross-sectional study in 995 participants in the Boston Puerto Rican Health Study | Plasma homocysteine concentratons | MTHFR (1298A > C and 677C > T polymorphisms) | Yes MTHFR genotypes with n-3 PUFA |
Dietary n-3 fatty acids modulate the effect of the MTHFR variants on plasma homocysteine. Participants with combined genotypes of both SNP who consumed high levels of n-3 PUFA had lower plasma homocysteine. |
| Richardson et al.(34) | Cross-sectional study in two replication cohorts: The Framingham study (1259 men and 1352 women) and the GOLDN Study (481 men and 513 women | Anthropometrics, lipids and glucose | Seven SNP in the PLIN4 gene: rs884164, rs1609717, rs7250947, rs8887, rs8102428, rs892158, and rs11673616. | Yes PLIN4 rs8887 and rs884164 |
n-3 fatty acids modulate the associations between the rs8887 SNP and anthropometrics. rs884164 showed interaction with both n3 and n6 PUFA modulating anthropometric and lipid phenotypes. |
PPARA: Peroxisome Proliferator-Activated Receptor alpha; APOA5: apolipoprotein A-V; ADIPOQ: Adiponectin; PPARG2: Peroxisome Proliferator-Activated Receptor-γ2; FADS: fatty acid desaturase; IL-6: Interleukin-6; MTHFR: Methylenetetrahydrofolate reductase; PLIN4: perilipin 4.