Table 1.
Common PPAR-α SNPs associated with metabolic phenotypes1
| SNP | Study population | Minor allele frequency, % | Metabolic effects | OR (95% CI) | P value | Ref. |
| L162V rs1800206 | 2373 subjects (1128 men and 1244 women) in the Framingham Offspring Study | 6.9 | Results observed in men | — | — | 79 |
| ↑ TC | — | 0.0012 | ||||
| ↑ LDL-C | — | 0.0004 | ||||
| ↑ ApoB | — | 0.009 | ||||
| In women | — | — | ||||
| ↑ ApoB | — | 0.03 | ||||
| 610 young healthy white subjects average age, 24 y) | 7.5 | Results observed in men | — | — | 80 | |
| ↑ TG | — | 0.0040 | ||||
| ↓ HDL | — | 0.0017 | ||||
| Danish study of middle-aged subjects (N = 5799; average age, 46 y) | 5.8 (95% CI: 5.4–6.2) | ↑ TG | — | 0.007 | 81 | |
| 59 healthy male students at the University of Cordoba (Spain), ranged from 18 to 49 y of age | 10.2 | ↑ TC | — | 0.003 | 73 | |
| ↑ LDL-C | — | 0.001 | ||||
| ↑ ApoB | — | 0.004 | ||||
| 2508 middle-age (50–61 y-old) healthy European men and 129 type 2 diabetic men and women (86 European, 43 Asian) | Europeans: 6.6 (95% CI: 3.0–10) | Results observed in subjects with type 2 diabetes | — | — | 69 | |
| Asians: 2.5 (95% CI: 0–6.0) | ↑ TC | — | 0.04 | |||
| ↑ ApoA1 | — | 0.003 | ||||
| 335 African Americans aged 30 y or older | 1.5 | ↑ ApoC2 | — | 0.0005 | 82 | |
| ↑ TG | — | 0.009 | ||||
| 570 subjects of an admixed population (147 males and 423 females) from Cuiaba City, Brazil | 5.2 | ↑ Dyslipidemia | 2.12 (1.0, 4.47) | 0.025, 0.0502 | 85 | |
| 767 subjects of the STOP-NIDDM trial (385 men and 382 women) | 7.0 | ↑ Development of type 2 diabetes | 1.93 (1.05, 3.58) | 0.035 | 74 | |
| 632 unrelated men from Quebec, Canada | 10.6 | Waist circumference (cm) is explain by PPAR-α–L162V × SFA interaction in 2.71% of variance | — | 0.01 | 78 | |
| 1003 men and 1103 women participating in the Framingham cohort | 6.98 | PPAR-α–L162V × low PUFA diet interaction | — | — | 102 | |
| ↑ TG | — | <0.05 | ||||
| ↑ ApoCIII | — | <0.05 | ||||
| PPAR-α–L162V × high PUFA diet interaction: | — | |||||
| ↓ TG | — | <0.05 | ||||
| ↓ ApoC3 | — | <0.05 | ||||
| 674 participants between 18 and 55 y of age; all subjects were recruited from the Quebec City metropolitan area | 8.8 | PPAR-α–L162V × high saturated fat intake interaction | — | — | 103 | |
| ↓ Peak particle diameters of LDL | — | 0.007 | ||||
| From 66 subjects from Quebec City metropolitan area, 20 healthy white men were selected, matched according to age and BMI | 10.6 | PPAR-α–162V × high PUFA diet interaction | — | — | 104 | |
| ↓ ApoA1 | — | 0.02 | ||||
| V227A rs1800234 | 401 apparently healthy subjects (207 men and 194 women), all Japanese | 5.1 | Results observed in women | — | — | 86 |
| ↓ TC | — | 0.046 | ||||
| ↓ TG | — | 0.038 | ||||
| 706 Japanese men | 5.0 | In nondrinker group | — | — | 70,90 | |
| ↓ TC | — | <0.05 | ||||
| ↓ TG | — | <0.05 | ||||
| 1964 men (1318 Chinese, 364 Malaysian, and 282 Asian Indians) and 2284 women (1581 Chinese, 397 Malaysian, and 306 Asian Indians) from the 1998 Singapore National Health Survey | 4.0 in Chinese 0.6 in Malays 0.3 in Asian Indians | PPAR-α–V227A × increasing dietary PUFA intake interaction in Chinese women | — | — | 88 | |
| ↓ HDL-C | — | 0.049 | ||||
| Intron 7G > C rs4253778 | 570 subjects from an admixed population (147 males and 423 females) from Cuiaba City, Brazil | 29.2 | ↑ Dyslipidemia | 1.56 (1.05, 2.33) | 0.027, 0.0292 | 85 |
| 1810 white subjects with type 2 diabetes from the prospective Go-DARTS | 18.2 (0.169–0.194) | ↑ TC | — | <0.05 | 83 | |
| ↑ HDL-C | — | <0.05 | ||||
| ↑ Risk of nonfatal myocardial infarction | 2.77,3 (1.34, 5.75), | 0.006 | ||||
| 358 white subjects (178 with a diagnosis of coronary artery disease and 180 without) | 15.5 | In the coronary artery disease group | — | — | 93 | |
| ↓ TC | — | 0.016 | ||||
| ↓ HDL-C | — | 0.029 | ||||
| 230 men from a hospital-based Indian population (110 patients with coronary artery disease and 120 healthy men) | 6.0 | ↑ Dyslipidemia | 2.95 (1.5, 4.39) | <0.05 | 94 | |
| 207 subjects with type 2 diabetes participating in the Diabetes Atherosclerosis Intervention Study (DAIS) | 11.9 | After fenofibrate treatment in patients with type 2 diabetes: | 3.10 (1.28, 7.52) | 0.012 | 119 | |
| ↓ TG | ||||||
| Haplotype of: rs135539, L162V, rs4253778 | 912 white subject with type 2 diabetes from 2 studies: UDACS and EDSC | 0.9 | ↑ onset of diabetes of type 2 diabetes, ∼10 y | 2.42 (0.70, 8.29) | 0.03 | 75 |
| 140+5435T > C rs135549 | 59 healthy male students at the University of Cordoba (Spain), age range,18–49 y e | 36.4 | Postprandial response with oral fat load (saturated fatty acids) | — | — | 73 |
| ↓ Small TRL-cholesterol | — | 0.039 | ||||
| ↓ Small TRL-TG | — | 0.008 | ||||
| 3′UTR G > A (rs6008259) | 10,134 white and 3480 African American subjects were selected from the ARIC study | 18.0 in whites, 67.0 in African Americans | PPAR-α 3′UTR G > A × linoleic acid intake interaction in white participants | — | — | 106 |
| ↓ TC | — | 0.03 | ||||
| ↓ LDL-C | — | 0.03 | ||||
| 3′UTR C > T (rs3892755) | 10,134 whites and 3480 African Americans were selected from the ARIC Study | 0.3 in whites, 28.5 in African Americans | PPAR-α-3′UTR C>T × long-chain n3 fatty acid intake in African Americans participants | — | — | 106 |
| ↓ TC | — | 0.03 | ||||
| ↓ LDL-C | — | 0.02 | ||||
| rs135550 | 861 subjects (white and nearly all of European ancestry) from GOLDN study | CEU4 20.0 | After fenofibrate treatment: | — | — | 121 |
| ↓ LDL-C | — | 0.001 | ||||
| rs9626730 | 861 subjects (white and nearly all of European ancestry) from GOLDN study | CEU4 14.2 | After fenofibrate treatment: | — | — | 121 |
| ↓ IL-2 | — | 0.0002 |
1
Apo, apolipoprotein; SNPs, single nucleotide polymorphisms; TC, total cholesterol; TG, triglyceride; TRL, triglyceride-rich lipoprotein.
2
P value adjusted for alcohol consumption and waist-to-hip ratio.
3
Hazard ratio.
4
White population from HapMap International Project (http://hapmap.ncbi.nlm.nih.gov/).